Exploration of Drug Science

Exploration of Drug Science

eISSN: 2836-7677

EiC: Fernando Albericio, PhD, Universidad de Barcelona and University of KwaZulu-Natal

Frequency: Bimonthly

APC: No Article Processing Charge

Publishing Model: Open Access

Peer Review Model: Single Blind

Indexing & Archiving: Portico

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Original Article

Heterogeneous graph convolutional neural network for protein-ligand scoring
Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and [...] Read more.

Aim:

Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.

Methods:

Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.

Results:

HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.

Conclusions:

Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.

Kevin Crampon ... Luiz Angelo Steffenel

Published: April 30, 2023 Explor Drug Sci. 2023;1:126–139
DOI: https://doi.org/10.37349/eds.2023.00010
This article belongs to the special issue Machine Learning for Drug Science

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Aim:

Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.

Methods:

Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.

Results:

HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.

Conclusions:

Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.

Open Access

Review

Focused ultrasound for treatment of peripheral brain tumors
Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) t [...] Read more.

Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

Phillip Mitchell Johansen ... Brandon Lucke-Wold

Published: April 28, 2023 Explor Drug Sci. 2023;1:107–125
DOI: https://doi.org/10.37349/eds.2023.00009

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Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

Open Access

Review

Nano theranostics involved in bladder cancer treatment
Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the inte [...] Read more.

Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.

Kunpeng Liu ... Qingsong Yu

Published: April 28, 2023 Explor Drug Sci. 2023;1:81–106
DOI: https://doi.org/10.37349/eds.2023.00008
This article belongs to the special issue Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

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Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.

Open Access

Editorial

Machine learning for drug science

Walter F. de Azevedo Jr.

Published: April 16, 2023 Explor Drug Sci. 2023;1:77–80
DOI: https://doi.org/10.37349/eds.2023.00007
This article belongs to the special issue Machine Learning for Drug Science

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Open Access

Original Article

Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo
Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, [...] Read more.

Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

Jia Li Guo ... Ji Zhong Zhao

Published: March 30, 2023 Explor Drug Sci. 2023;1:64–76
DOI: https://doi.org/10.37349/eds.2023.00006
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

Open Access

Systematic Review

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data
Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present o [...] Read more.

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Sai Batchu ... Brandon Lucke-Wold

Published: February 28, 2023 Explor Drug Sci. 2023;1:55–63
DOI: https://doi.org/10.37349/eds.2023.00005

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Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Archives Current Issue

Open Access

Editorial

Drug discovery: a multifactorial ecosystem

Fernando Albericio

Published: January 01, 2023 Explor Drug Sci. 2023;1:1–5
DOI: https://doi.org/10.37349/eds.2022.00001

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Open Access

Review

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins
It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell [...] Read more.

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Qiushi Chen ... Xuechen Li

Published: February 28, 2023 Explor Drug Sci. 2023;1:31–54
DOI: https://doi.org/10.37349/eds.2023.00004
This article belongs to the special issue Bioactive Peptides discovery and development

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It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Open Access

Systematic Review

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data
Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present o [...] Read more.

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Sai Batchu ... Brandon Lucke-Wold

Published: February 28, 2023 Explor Drug Sci. 2023;1:55–63
DOI: https://doi.org/10.37349/eds.2023.00005

Full Text

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View:254

Download:15

Times Cited: 0

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Open Access

Original Article

Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo
Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, [...] Read more.

Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

Jia Li Guo ... Ji Zhong Zhao

Published: March 30, 2023 Explor Drug Sci. 2023;1:64–76
DOI: https://doi.org/10.37349/eds.2023.00006
This article belongs to the special issue Exploring Potential Drugs from Natural Products

Full Text

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View:240

Download:13

Times Cited: 0

Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

Open Access

Original Article

Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment
Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) [...] Read more.

Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Yi Ouyang ... Hui Liu

Published: February 27, 2023 Explor Drug Sci. 2023;1:18–30
DOI: https://doi.org/10.37349/eds.2023.00003
This article belongs to the special issue Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

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Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Open Access

Review

Focused ultrasound for treatment of peripheral brain tumors
Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) t [...] Read more.

Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

Phillip Mitchell Johansen ... Brandon Lucke-Wold

Published: April 28, 2023 Explor Drug Sci. 2023;1:107–125
DOI: https://doi.org/10.37349/eds.2023.00009

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Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

Archives Current Issue

Open Access

Editorial

Drug discovery: a multifactorial ecosystem

Fernando Albericio

Published: January 01, 2023 Explor Drug Sci. 2023;1:1–5
DOI: https://doi.org/10.37349/eds.2022.00001

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Open Access

Review

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins
It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell [...] Read more.

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Qiushi Chen ... Xuechen Li

Published: February 28, 2023 Explor Drug Sci. 2023;1:31–54
DOI: https://doi.org/10.37349/eds.2023.00004
This article belongs to the special issue Bioactive Peptides discovery and development

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It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Open Access

Original Article

Heterogeneous graph convolutional neural network for protein-ligand scoring
Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and [...] Read more.

Aim:

Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.

Methods:

Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.

Results:

HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.

Conclusions:

Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.

Kevin Crampon ... Luiz Angelo Steffenel

Published: April 30, 2023 Explor Drug Sci. 2023;1:126–139
DOI: https://doi.org/10.37349/eds.2023.00010
This article belongs to the special issue Machine Learning for Drug Science

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Aim:

Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.

Methods:

Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.

Results:

HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.

Conclusions:

Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.

Open Access

Original Article

Convenient estimation of oxytetracycline and polymyxin B by a novel high-performance liquid chromatography method: development and validation
Aim: The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and pol [...] Read more.

Aim:

The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.

Methods:

The HPLC assay method was validated on X-Bridge C₁₈ [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.

Results:

The method was found to be linear with a concentration range of 5–25 μg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per International Conference on Harmonization (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin^® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.

Conclusions:

Linear CC were obtained with a correlation coefficient (R² > 0.99) with acceptable results of accuracy and precision.

Graphical abstract.
Ultraviolet visible and HPLC method development

Tanu Chaudhary ... Dilpreet Singh

Published: February 24, 2023 Explor Drug Sci. 2023;1:6–17
DOI: https://doi.org/10.37349/eds.2023.00002

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Aim:

The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.

Methods:

The HPLC assay method was validated on X-Bridge C₁₈ [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.

Results:

The method was found to be linear with a concentration range of 5–25 μg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per International Conference on Harmonization (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin^® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.

Conclusions:

Linear CC were obtained with a correlation coefficient (R² > 0.99) with acceptable results of accuracy and precision.

Graphical abstract.
Ultraviolet visible and HPLC method development

Open Access

Systematic Review

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data
Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present o [...] Read more.

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Sai Batchu ... Brandon Lucke-Wold

Published: February 28, 2023 Explor Drug Sci. 2023;1:55–63
DOI: https://doi.org/10.37349/eds.2023.00005

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View:254

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Times Cited: 0

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Open Access

Original Article

Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment
Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) [...] Read more.

Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Yi Ouyang ... Hui Liu

Published: February 27, 2023 Explor Drug Sci. 2023;1:18–30
DOI: https://doi.org/10.37349/eds.2023.00003
This article belongs to the special issue Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

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Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Archives Current Issue

Open Access

Editorial

Drug discovery: a multifactorial ecosystem

Fernando Albericio

Published: January 01, 2023 Explor Drug Sci. 2023;1:1–5
DOI: https://doi.org/10.37349/eds.2022.00001

Full Text

PDF

View:602

Download:52

Times Cited: 0

Open Access

Original Article

Convenient estimation of oxytetracycline and polymyxin B by a novel high-performance liquid chromatography method: development and validation
Aim: The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and pol [...] Read more.

Aim:

The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.

Methods:

The HPLC assay method was validated on X-Bridge C₁₈ [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.

Results:

The method was found to be linear with a concentration range of 5–25 μg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per International Conference on Harmonization (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin^® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.

Conclusions:

Linear CC were obtained with a correlation coefficient (R² > 0.99) with acceptable results of accuracy and precision.

Graphical abstract.
Ultraviolet visible and HPLC method development

Tanu Chaudhary ... Dilpreet Singh

Published: February 24, 2023 Explor Drug Sci. 2023;1:6–17
DOI: https://doi.org/10.37349/eds.2023.00002

Full Text

PDF

View:151

Download:16

Times Cited: 0

Aim:

The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.

Methods:

The HPLC assay method was validated on X-Bridge C₁₈ [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.

Results:

The method was found to be linear with a concentration range of 5–25 μg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per International Conference on Harmonization (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin^® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.

Conclusions:

Linear CC were obtained with a correlation coefficient (R² > 0.99) with acceptable results of accuracy and precision.

Graphical abstract.
Ultraviolet visible and HPLC method development

Open Access

Original Article

Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment
Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) [...] Read more.

Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Yi Ouyang ... Hui Liu

Published: February 27, 2023 Explor Drug Sci. 2023;1:18–30
DOI: https://doi.org/10.37349/eds.2023.00003
This article belongs to the special issue Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

Full Text

PDF

View:219

Download:14

Times Cited: 0

Aim:

The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.

Methods:

MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO₂) coating to construct MPDA-CPT-MnO₂ nanocomposites.

Results:

When uptaken by tumor cells, the nanocomposites can degrade to produce O₂, release CPT, and generate manganese (Mn²⁺) under the stimulation of hydrogen peroxide (H₂O₂) and acid. The released CPT and Mn²⁺ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn²⁺-mediated Fenton-like reaction. After that, the generated Mn⁴⁺ can react with glutathione (GSH) through redox reaction to produce Mn²⁺ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.

Conclusions:

The developed MPDA-CPT-MnO₂ nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Open Access

Review

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins
It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell [...] Read more.

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Qiushi Chen ... Xuechen Li

Published: February 28, 2023 Explor Drug Sci. 2023;1:31–54
DOI: https://doi.org/10.37349/eds.2023.00004
This article belongs to the special issue Bioactive Peptides discovery and development

Full Text

PDF

View:355

Download:23

Times Cited: 0

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

Open Access

Systematic Review

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data
Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present o [...] Read more.

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Sai Batchu ... Brandon Lucke-Wold

Published: February 28, 2023 Explor Drug Sci. 2023;1:55–63
DOI: https://doi.org/10.37349/eds.2023.00005

Full Text

PDF

View:254

Download:15

Times Cited: 0

Aim:

Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods:

The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results:

It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions:

The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Open Access

Original Article

Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo
Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, [...] Read more.

Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

Jia Li Guo ... Ji Zhong Zhao

Published: March 30, 2023 Explor Drug Sci. 2023;1:64–76
DOI: https://doi.org/10.37349/eds.2023.00006
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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Aim:

In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).

Methods:

Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.

Results:

The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.

Conclusions:

LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.

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Preventive and Therapeutic Potential of Nutraceuticals in Non-communicable Diseases

Prof. Marcello Iriti

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Drug Discovery in Neuropsychiatric Diseases: therapeutic opportunities beyond the classic aminergic system

Prof. Santiago J. Ballaz Prof. Fernando Albericio

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Prof. Xuechen Li

Submission Deadline: June 30, 2023

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Machine Learning for Drug Science

Prof. Walter Filgueira de Azevedo Jr.

Submission Deadline: May 31, 2023

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Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

Prof. Xiangyang Shi

Submission Deadline: June 30, 2023

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Exploring Potential Drugs from Natural Products

Prof. Juergen Reichardt

Submission Deadline: March 31, 2023

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From the Editor-in-Chief

The journey from the idea in the laboratory to the drug on the market is possibly the most exciting scientific process and, at the same time, the one with the most significant impact from both social and economic point of view. On the one hand, a new drug helps restore health and improves well-being, even saving lives, but it requires many years of work (an average of 15 years) and a large investment. Exploration of Drug Science (EDS) was born with the idea of covering all the steps of this often magical process, from the discovery itself, the preclinical phase, to the clinical phase. As the new Editor-in-Chief of EDS, I would like to invite colleagues to use our platform to share their latest findings with the scientific committee.
Fernando Albericio
Editor-in-Chief of Exploration of Drug Science

Exploration of Drug Science

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