Previous
Antimicrobial resistance (AMR) poses a growing global health threat, progressively undermining the clinical effectiveness of conventional antibiotic therapies. Despite their proven efficacy and standardized clinical frameworks, antibiotics exert strong selective pressures that accelerate resistance, disrupt host microbiota, and limit treatment options for chronic, biofilm-associated, and multidrug-resistant infections. Bacteriophage therapy has re-emerged as a potential adjunct or alternative approach, offering pathogen-specific antibacterial activity, preservation of commensal microbiota, and the capacity for co-evolution with bacterial hosts. This focused review critically compares antibiotics and bacteriophage therapy across mechanistic foundations, preclinical and clinical evidence, translational readiness, and real-world implementation challenges. While preclinical models consistently demonstrate robust antibacterial activity of bacteriophages, clinical evidence remains heterogeneous, with few randomized controlled studies available. Key system-level barriers, including regulatory inconsistency, manufacturing complexity, and lack of standardization, currently limit widespread clinical integration. Rather than positioning bacteriophages as replacements for antibiotics, this review emphasizes their potential role as complementary agents, particularly through bacteriophage-antibiotic synergy, to enhance treatment efficacy and mitigate resistance. Addressing methodological gaps, standardizing clinical trial designs, and developing integrated stewardship models will be critical to defining the future role of bacteriophage therapy in modern infectious disease management.
Antimicrobial resistance (AMR) poses a growing global health threat, progressively undermining the clinical effectiveness of conventional antibiotic therapies. Despite their proven efficacy and standardized clinical frameworks, antibiotics exert strong selective pressures that accelerate resistance, disrupt host microbiota, and limit treatment options for chronic, biofilm-associated, and multidrug-resistant infections. Bacteriophage therapy has re-emerged as a potential adjunct or alternative approach, offering pathogen-specific antibacterial activity, preservation of commensal microbiota, and the capacity for co-evolution with bacterial hosts. This focused review critically compares antibiotics and bacteriophage therapy across mechanistic foundations, preclinical and clinical evidence, translational readiness, and real-world implementation challenges. While preclinical models consistently demonstrate robust antibacterial activity of bacteriophages, clinical evidence remains heterogeneous, with few randomized controlled studies available. Key system-level barriers, including regulatory inconsistency, manufacturing complexity, and lack of standardization, currently limit widespread clinical integration. Rather than positioning bacteriophages as replacements for antibiotics, this review emphasizes their potential role as complementary agents, particularly through bacteriophage-antibiotic synergy, to enhance treatment efficacy and mitigate resistance. Addressing methodological gaps, standardizing clinical trial designs, and developing integrated stewardship models will be critical to defining the future role of bacteriophage therapy in modern infectious disease management.
DOI: https://doi.org/10.37349/eds.2026.1008159
Aim:
The iridium(III) [Ir(III)] complexes exhibit anticancer properties, and along with their photoluminescence properties, they can be employed as diagnostic agents. Hence, we have tried to evaluate both properties. For this, the complexes of Ir(III) with pyridyl-based heterocyclic ligands, viz., [(TPQ)3Ir] (
Methods:
These complexes were authenticated by NMR (1H and 13C{1H}) spectroscopy and high-resolution mass spectrometry (HRMS). Their photophysical properties were evaluated by UV-Vis spectroscopy and photoluminescence studies. Among them, [(TPQ)3Ir] (
Results:
Among these Ir(III) complexes (
Conclusions:
The [(TPQ)2Ir(4-EO2-pic)] (
Aim:
The iridium(III) [Ir(III)] complexes exhibit anticancer properties, and along with their photoluminescence properties, they can be employed as diagnostic agents. Hence, we have tried to evaluate both properties. For this, the complexes of Ir(III) with pyridyl-based heterocyclic ligands, viz., [(TPQ)3Ir] (
Methods:
These complexes were authenticated by NMR (1H and 13C{1H}) spectroscopy and high-resolution mass spectrometry (HRMS). Their photophysical properties were evaluated by UV-Vis spectroscopy and photoluminescence studies. Among them, [(TPQ)3Ir] (
Results:
Among these Ir(III) complexes (
Conclusions:
The [(TPQ)2Ir(4-EO2-pic)] (
DOI: https://doi.org/10.37349/eds.2026.1008158
Aim:
Chitosan (CHS)-based nanoparticulate systems have gained much interest due to their high drug loading capacity and the simplicity of their fabrication. The physical properties of two types of curcumin-loaded CHS nanoparticles (CHS-NPs) were determined and compared. A new in-vitro release method was developed based on mathematical modeling in which the drug is first released from the NP into the surrounding medium and subsequently diffuses through the membrane.
Methods:
Curcumin-loaded CHS-NPs were fabricated by ionotropic gelation using sodium tripolyphosphate (TPP) and sodium hexametaphosphate (SHMP) crosslinking, and characterized by NP tracking analysis, loading capacity, zeta potential, Fourier transform infrared spectroscopy (FTIR), and in-vitro release rates.
Results:
The data showed that compared to SHMP crosslinked CHS-NPs, TPP crosslinking demonstrated a decrease in entrapment efficiency at a relatively high concentration of the agent, probably by narrowing the space between the polymeric chains. As indicated by zeta potential measurements, TPP crosslinking at all levels was more uniformly distributed inside the NPs, whereas the higher molecular weight SHMP at a low concentration creates NPs mostly by binding onto the surface. It was found that the release rates of curcumin from CHS-NPs crosslinked by SHMP at higher concentrations were about twice as high as the release rates of curcumin from TPP-crosslinked CHS-NPs, accompanied by notable lag times.
Conclusions:
This significant increase in the release rates of curcumin from SHMP-crosslinked CHS-NPs is explained by the large spatial structure of this crosslinker compared to the small TPP molecules. This study advances the literature on drug diffusion by making it possible to accurately determine its release from nanoparticulate systems.
Aim:
Chitosan (CHS)-based nanoparticulate systems have gained much interest due to their high drug loading capacity and the simplicity of their fabrication. The physical properties of two types of curcumin-loaded CHS nanoparticles (CHS-NPs) were determined and compared. A new in-vitro release method was developed based on mathematical modeling in which the drug is first released from the NP into the surrounding medium and subsequently diffuses through the membrane.
Methods:
Curcumin-loaded CHS-NPs were fabricated by ionotropic gelation using sodium tripolyphosphate (TPP) and sodium hexametaphosphate (SHMP) crosslinking, and characterized by NP tracking analysis, loading capacity, zeta potential, Fourier transform infrared spectroscopy (FTIR), and in-vitro release rates.
Results:
The data showed that compared to SHMP crosslinked CHS-NPs, TPP crosslinking demonstrated a decrease in entrapment efficiency at a relatively high concentration of the agent, probably by narrowing the space between the polymeric chains. As indicated by zeta potential measurements, TPP crosslinking at all levels was more uniformly distributed inside the NPs, whereas the higher molecular weight SHMP at a low concentration creates NPs mostly by binding onto the surface. It was found that the release rates of curcumin from CHS-NPs crosslinked by SHMP at higher concentrations were about twice as high as the release rates of curcumin from TPP-crosslinked CHS-NPs, accompanied by notable lag times.
Conclusions:
This significant increase in the release rates of curcumin from SHMP-crosslinked CHS-NPs is explained by the large spatial structure of this crosslinker compared to the small TPP molecules. This study advances the literature on drug diffusion by making it possible to accurately determine its release from nanoparticulate systems.
DOI: https://doi.org/10.37349/eds.2026.1008157
Aim:
Bisoprolol fumarate (BF), commonly prescribed for cardiovascular conditions, is usually split to achieve specific doses. This study evaluated the effects of tablet splitting on the quality parameters of scored BF tablets from three different brands marketed in Saudi Arabia.
Methods:
The products were evaluated for weight variation, content uniformity, and dissolution for intact and split tablets. A UPLC-sensitive assay was used for drug quantification.
Results:
The results showed that all products lost less than 3% of its weight upon splitting, meeting the USP requirements. Content uniformity was between 85% and 115% for all products, complying with pharmacopoeial standards. Dissolution studies showed some variation between intact and split tablets. The f2 similarity factor was calculated to compare the dissolution profiles of BF from both forms. The f2 values showed a similar dissolution profile for the innovator product (f2 was 62.53), but dissimilar profiles for Generic-1 and -2 (f2 values were 48.90 and 34.43, respectively).
Conclusions:
These results should be taken into consideration by healthcare professionals to avoid sub-therapeutic or toxic effects resulting from tablet splitting.
Aim:
Bisoprolol fumarate (BF), commonly prescribed for cardiovascular conditions, is usually split to achieve specific doses. This study evaluated the effects of tablet splitting on the quality parameters of scored BF tablets from three different brands marketed in Saudi Arabia.
Methods:
The products were evaluated for weight variation, content uniformity, and dissolution for intact and split tablets. A UPLC-sensitive assay was used for drug quantification.
Results:
The results showed that all products lost less than 3% of its weight upon splitting, meeting the USP requirements. Content uniformity was between 85% and 115% for all products, complying with pharmacopoeial standards. Dissolution studies showed some variation between intact and split tablets. The f2 similarity factor was calculated to compare the dissolution profiles of BF from both forms. The f2 values showed a similar dissolution profile for the innovator product (f2 was 62.53), but dissimilar profiles for Generic-1 and -2 (f2 values were 48.90 and 34.43, respectively).
Conclusions:
These results should be taken into consideration by healthcare professionals to avoid sub-therapeutic or toxic effects resulting from tablet splitting.
DOI: https://doi.org/10.37349/eds.2026.1008156
Antibodies currently represent a leading segment of the biopharmaceutical market and are expected to maintain a significant presence in the therapeutic landscape. Development of therapeutic antibodies represents one of the most transformative advances in the modern medicine field, with hundreds of successful products on the market that have changed the lives of millions and the history of mankind by revolutionizing medical treatment. In its broadest context, antibody-based products consist of full-length antibodies, antibody fragments, polyvalent and polyspecific antibodies, and their conjugates (for targeted delivery of other therapeutic drugs/agents). High target specificity, tailored mechanisms of action, and broad applicability have made antibodies indispensable in a variety of diseases. With advancements in protein engineering as well as growing integration of computational biology, the field of antibody development continues to push boundaries and is expected to drive the next era of breakthroughs. This article charts the journey of therapeutic antibodies from their conceptual roots to their central role in current medicine, and offers a forward-looking perspective on what lies ahead in this dynamic field.
Antibodies currently represent a leading segment of the biopharmaceutical market and are expected to maintain a significant presence in the therapeutic landscape. Development of therapeutic antibodies represents one of the most transformative advances in the modern medicine field, with hundreds of successful products on the market that have changed the lives of millions and the history of mankind by revolutionizing medical treatment. In its broadest context, antibody-based products consist of full-length antibodies, antibody fragments, polyvalent and polyspecific antibodies, and their conjugates (for targeted delivery of other therapeutic drugs/agents). High target specificity, tailored mechanisms of action, and broad applicability have made antibodies indispensable in a variety of diseases. With advancements in protein engineering as well as growing integration of computational biology, the field of antibody development continues to push boundaries and is expected to drive the next era of breakthroughs. This article charts the journey of therapeutic antibodies from their conceptual roots to their central role in current medicine, and offers a forward-looking perspective on what lies ahead in this dynamic field.
DOI: https://doi.org/10.37349/eds.2026.1008155
Intranasal drug delivery exhibits therapeutic potential for the treatment of central nervous system (CNS) diseases, as it allows pharmaceuticals to bypass the blood-brain barrier (BBB) via the olfactory and trigeminal pathways. The primary advantage of this method lies in its non-invasiveness and low systemic toxicity. Nevertheless, this delivery method faces notable challenges, including limited nasal mucosal absorption and short residence time in the olfactory region. To address these limitations, intranasal nanomedicine has gained research attention. Nanomedicines can improve brain bioavailability by enhancing drug solubility, permeability, and stability. The following discussion summarizes recent advancements in nanotechnology-enabled nose-to-brain delivery systems, with the aim of synthesizing progress in the field and outlining future research directions.
Intranasal drug delivery exhibits therapeutic potential for the treatment of central nervous system (CNS) diseases, as it allows pharmaceuticals to bypass the blood-brain barrier (BBB) via the olfactory and trigeminal pathways. The primary advantage of this method lies in its non-invasiveness and low systemic toxicity. Nevertheless, this delivery method faces notable challenges, including limited nasal mucosal absorption and short residence time in the olfactory region. To address these limitations, intranasal nanomedicine has gained research attention. Nanomedicines can improve brain bioavailability by enhancing drug solubility, permeability, and stability. The following discussion summarizes recent advancements in nanotechnology-enabled nose-to-brain delivery systems, with the aim of synthesizing progress in the field and outlining future research directions.
DOI: https://doi.org/10.37349/eds.2026.1008154
This article belongs to the special issue Nanoformulations for Non-Intravenous Drug Delivery
DOI: https://doi.org/10.37349/eds.2026.1008153
Ageing is a gradual, multifactorial process that leads to the deterioration of physical and mental health, increasing the risk of disease and eventually death. Indicators of ageing manifest at the molecular level, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, and dysregulation of key signalling pathways such as the mechanistic target of rapamycin (mTOR) and insulin signalling. These molecular hallmarks of ageing are interconnected, amplifying one another over time. The resulting cellular stress triggers apoptosis or drives cells into a pathological state known as cellular senescence, in which they secrete inflammatory, pro-ageing factors. Consequently, there is a progressive decline in tissue function and regenerative capacity, accompanied by atrophy and stem cell exhaustion under a chronically inflamed microenvironment. Although functional decline with age is irreversible, research indicates it can be delayed. In this review, we discuss the hallmarks of ageing, conventional pharmacological interventions with demonstrated anti-ageing effects in cellular and animal models, and emerging therapeutic strategies being explored as ageing becomes increasingly recognized as a major risk factor for disease development.
Ageing is a gradual, multifactorial process that leads to the deterioration of physical and mental health, increasing the risk of disease and eventually death. Indicators of ageing manifest at the molecular level, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, and dysregulation of key signalling pathways such as the mechanistic target of rapamycin (mTOR) and insulin signalling. These molecular hallmarks of ageing are interconnected, amplifying one another over time. The resulting cellular stress triggers apoptosis or drives cells into a pathological state known as cellular senescence, in which they secrete inflammatory, pro-ageing factors. Consequently, there is a progressive decline in tissue function and regenerative capacity, accompanied by atrophy and stem cell exhaustion under a chronically inflamed microenvironment. Although functional decline with age is irreversible, research indicates it can be delayed. In this review, we discuss the hallmarks of ageing, conventional pharmacological interventions with demonstrated anti-ageing effects in cellular and animal models, and emerging therapeutic strategies being explored as ageing becomes increasingly recognized as a major risk factor for disease development.
DOI: https://doi.org/10.37349/eds.2026.1008152
The significant medicinal constituents and pharmacological potential of several botanicals suggest promising therapeutic applications. Scorzonera undulata displayed a diverse phytochemical profile, with 25 volatile and 21 phenolic compounds identified, including quinic and chlorogenic acids, along with flavonoids such as kaempferol, apigenin, luteolin derivatives, quercitrin, and naringin—mostly concentrated in the aerial parts. These extracts exhibited notable antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activities, especially methanolic extracts against MCF-7 breast cancer cells, indicating therapeutic relevance. Andrographis paniculata extracts, rich in andrographolide, showed clinical potential in alleviating mild COVID-19 symptoms. However, the compound’s nonlinear pharmacokinetics highlight the need for optimized delivery strategies. Morinda citrifolia fruit extracts demonstrated considerable in vitro antimicrobial effects and moderate cytotoxicity, supported by UPLC–Orbitrap MS identification of unique bioactives. These findings reinforce the need for further pharmacological and clinical validation. The antiviral efficacy of Houttuynia cordata against dengue virus type 2 was evident, with aqueous extracts showing strong virucidal action and inhibition of viral replication. Hyperoside was identified as the dominant active constituent, supported by a rich phytochemical profile including flavonoids, aristolactams, and triterpenoids. Genotoxicity assessments indicated a favorable safety profile, suggesting potential for phytotherapeutic development. Achillea millefolium (yarrow) contained essential oils enriched in camphor, 1,8-cineole, artemisia ketone, and azulene derivatives, alongside phenolic acids and flavonoids like chlorogenic acid, apigenin, luteolin, and quercetin. These contributed to its antioxidant, anti-inflammatory, antimicrobial, and hemostatic effects, validating traditional medicinal applications and warranting clinical standardization. Flavonoids such as luteolin and apigenin offered anticancer and cardiovascular benefits by inhibiting PD-L1 via STAT3 suppression and promoting autophagy to counter vascular calcification. Bryophyllum pinnatum demonstrated broad pharmacological activity attributed to bufadienolides, flavonoids, and phenolic acids, supporting its ethnomedicinal use while emphasizing the need for clinical safety validation.
The significant medicinal constituents and pharmacological potential of several botanicals suggest promising therapeutic applications. Scorzonera undulata displayed a diverse phytochemical profile, with 25 volatile and 21 phenolic compounds identified, including quinic and chlorogenic acids, along with flavonoids such as kaempferol, apigenin, luteolin derivatives, quercitrin, and naringin—mostly concentrated in the aerial parts. These extracts exhibited notable antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activities, especially methanolic extracts against MCF-7 breast cancer cells, indicating therapeutic relevance. Andrographis paniculata extracts, rich in andrographolide, showed clinical potential in alleviating mild COVID-19 symptoms. However, the compound’s nonlinear pharmacokinetics highlight the need for optimized delivery strategies. Morinda citrifolia fruit extracts demonstrated considerable in vitro antimicrobial effects and moderate cytotoxicity, supported by UPLC–Orbitrap MS identification of unique bioactives. These findings reinforce the need for further pharmacological and clinical validation. The antiviral efficacy of Houttuynia cordata against dengue virus type 2 was evident, with aqueous extracts showing strong virucidal action and inhibition of viral replication. Hyperoside was identified as the dominant active constituent, supported by a rich phytochemical profile including flavonoids, aristolactams, and triterpenoids. Genotoxicity assessments indicated a favorable safety profile, suggesting potential for phytotherapeutic development. Achillea millefolium (yarrow) contained essential oils enriched in camphor, 1,8-cineole, artemisia ketone, and azulene derivatives, alongside phenolic acids and flavonoids like chlorogenic acid, apigenin, luteolin, and quercetin. These contributed to its antioxidant, anti-inflammatory, antimicrobial, and hemostatic effects, validating traditional medicinal applications and warranting clinical standardization. Flavonoids such as luteolin and apigenin offered anticancer and cardiovascular benefits by inhibiting PD-L1 via STAT3 suppression and promoting autophagy to counter vascular calcification. Bryophyllum pinnatum demonstrated broad pharmacological activity attributed to bufadienolides, flavonoids, and phenolic acids, supporting its ethnomedicinal use while emphasizing the need for clinical safety validation.
DOI: https://doi.org/10.37349/eds.2026.1008151
Aim:
A seven amino acid cyclic peptide has been applied to human blood plasma treated with glucose metabolite methylglyoxal (MG) in “proof of concept” experiments to determine the peptide’s ability to counteract pathologies associated with hyperglycemia. Similar pathologies are evident during aging and in age-related disorders. In fact, elevated MG levels in the blood lead directly to diabetic complications and accelerated aging, including cognitive decline. These changes are attributed to oxidant stress and amyloidogenesis, the latter involving toxic accumulations of blood and tissue proteins.
Methods:
cSKE7 was redesigned from cell survival-promoting and anti-inflammatory fragments near the N-terminus of human/primate “orphan” protein DSEP/Dermcidin and incubated at low micromolar concentrations with the MG-stressed human plasma for 24 hours. The modified design of the new compound offers several practical advantages over predecessors including cyclic stability and a marked increase in aqueous solubility.
Results:
The peptide dispersed thioflavin-T-stained amyloid aggregates and reduced oxidant stress as measured by plasma levels of free thiols and of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Since these N-terminal fragments of DSEP/Dermcidin have been shown to bind and influence the activity of heat shock protein 70 (HSP70), HSP70 inhibitor pifithrin-μ was added to the plasma prior to peptide treatment. The inhibitor disrupted amyloid dispersion and both peptide-induced and, in some cases, normally occurring antioxidant effects, suggesting these reparative activities are HSP70 dependent.
Conclusions:
The results are discussed in terms of their potential use in new therapies for the complications of metabolic disease and disorders of aging that result from a deterioration of the quality control mechanisms of proteostasis.
Aim:
A seven amino acid cyclic peptide has been applied to human blood plasma treated with glucose metabolite methylglyoxal (MG) in “proof of concept” experiments to determine the peptide’s ability to counteract pathologies associated with hyperglycemia. Similar pathologies are evident during aging and in age-related disorders. In fact, elevated MG levels in the blood lead directly to diabetic complications and accelerated aging, including cognitive decline. These changes are attributed to oxidant stress and amyloidogenesis, the latter involving toxic accumulations of blood and tissue proteins.
Methods:
cSKE7 was redesigned from cell survival-promoting and anti-inflammatory fragments near the N-terminus of human/primate “orphan” protein DSEP/Dermcidin and incubated at low micromolar concentrations with the MG-stressed human plasma for 24 hours. The modified design of the new compound offers several practical advantages over predecessors including cyclic stability and a marked increase in aqueous solubility.
Results:
The peptide dispersed thioflavin-T-stained amyloid aggregates and reduced oxidant stress as measured by plasma levels of free thiols and of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Since these N-terminal fragments of DSEP/Dermcidin have been shown to bind and influence the activity of heat shock protein 70 (HSP70), HSP70 inhibitor pifithrin-μ was added to the plasma prior to peptide treatment. The inhibitor disrupted amyloid dispersion and both peptide-induced and, in some cases, normally occurring antioxidant effects, suggesting these reparative activities are HSP70 dependent.
Conclusions:
The results are discussed in terms of their potential use in new therapies for the complications of metabolic disease and disorders of aging that result from a deterioration of the quality control mechanisms of proteostasis.
DOI: https://doi.org/10.37349/eds.2026.1008150
This article belongs to the special issue Peptide Science Without Borders: Novel Insights for Drug Discovery
The s-triazine scaffold has emerged as a privileged heterocyclic nucleus/moiety in pharmaceutical discovery and development, owing to its presence in several natural products and clinically relevant therapeutic agents, including enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. s-Triazine derivatives are not only economically accessible and synthetically versatile, but they also exhibit a broad spectrum of noteworthy biological activities, encompassing anticancer, anti-inflammatory, antiviral, antidiabetic, anticonvulsant, antitubercular, and antimicrobial properties. Their widespread utility is further supported by the ease of synthesis from inexpensive precursors such as amidines or the readily available 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), which enables sequential functionalization and the rapid generation of diverse analogues. The heightened reactivity and modularity of the s-triazine core have facilitated the development of structurally rich heterocyclic hybrids with enhanced potency and improved pharmacological profiles. These multitarget-directed systems offer exciting opportunities for addressing various forms of cancer. Considering the increasing pace of innovation in this field, a comprehensive overview of recent advancements in s-triazine-based hybrid molecules is both timely and necessary. This review highlights current progress, key design strategies, and emerging perspectives to inspire continued efforts toward the identification of promising s-triazine-based lead candidates for future drug development as anticancer agents.
The s-triazine scaffold has emerged as a privileged heterocyclic nucleus/moiety in pharmaceutical discovery and development, owing to its presence in several natural products and clinically relevant therapeutic agents, including enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. s-Triazine derivatives are not only economically accessible and synthetically versatile, but they also exhibit a broad spectrum of noteworthy biological activities, encompassing anticancer, anti-inflammatory, antiviral, antidiabetic, anticonvulsant, antitubercular, and antimicrobial properties. Their widespread utility is further supported by the ease of synthesis from inexpensive precursors such as amidines or the readily available 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), which enables sequential functionalization and the rapid generation of diverse analogues. The heightened reactivity and modularity of the s-triazine core have facilitated the development of structurally rich heterocyclic hybrids with enhanced potency and improved pharmacological profiles. These multitarget-directed systems offer exciting opportunities for addressing various forms of cancer. Considering the increasing pace of innovation in this field, a comprehensive overview of recent advancements in s-triazine-based hybrid molecules is both timely and necessary. This review highlights current progress, key design strategies, and emerging perspectives to inspire continued efforts toward the identification of promising s-triazine-based lead candidates for future drug development as anticancer agents.
DOI: https://doi.org/10.37349/eds.2026.1008149
This article belongs to the special issue The Role of Triazine Scaffolds in Modern Drug Development
Aim:
To evaluate the real-world effectiveness of prophylactic metoclopramide in preventing opioid-induced nausea and vomiting (OINV) during the initial phase of strong opioid therapy in opioid-naïve patients with cancer-related pain.
Methods:
This retrospective, single-center observational cohort study included adult patients with pathologically confirmed malignancies who initiated strong opioid therapy between January 2023 and December 2024. Patients were categorized into a prophylactic metoclopramide group or a no-prophylaxis control group. Complete control (CC) of OINV during the first 7 days was defined as the absence of nausea, vomiting, and rescue antiemetic use. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CC, adjusting for age, sex, body mass index, cancer subtype, cancer stage, comorbidity status, and morphine-equivalent daily dose (MEDD). Subgroup analyses were conducted based on age, sex, and cancer subtype.
Results:
A total of 244 patients were included, of whom 199 received prophylactic metoclopramide, and 45 received no prophylaxis. The prophylactic group achieved significantly higher CC rates than the control group (74.9% vs. 37.8%, p < 0.001). Multivariate logistic regression confirmed that prophylactic metoclopramide was independently associated with higher odds of achieving CC (adjusted OR = 0.20, 95% CI: 0.10–0.40; p < 0.001). Similar improvements were observed for nausea and vomiting control. Subgroup analyses demonstrated consistent benefits across age and sex groups, with particularly notable effects in patients with gastrointestinal cancers.
Conclusions:
Prophylactic metoclopramide significantly improves OINV control in opioid-naïve patients with cancer-related pain during the initiation of strong opioids. These findings support the rational use of early antiemetic prophylaxis in routine clinical practice. Prospective randomized trials are warranted to validate these real-world results and assess long-term safety.
Aim:
To evaluate the real-world effectiveness of prophylactic metoclopramide in preventing opioid-induced nausea and vomiting (OINV) during the initial phase of strong opioid therapy in opioid-naïve patients with cancer-related pain.
Methods:
This retrospective, single-center observational cohort study included adult patients with pathologically confirmed malignancies who initiated strong opioid therapy between January 2023 and December 2024. Patients were categorized into a prophylactic metoclopramide group or a no-prophylaxis control group. Complete control (CC) of OINV during the first 7 days was defined as the absence of nausea, vomiting, and rescue antiemetic use. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CC, adjusting for age, sex, body mass index, cancer subtype, cancer stage, comorbidity status, and morphine-equivalent daily dose (MEDD). Subgroup analyses were conducted based on age, sex, and cancer subtype.
Results:
A total of 244 patients were included, of whom 199 received prophylactic metoclopramide, and 45 received no prophylaxis. The prophylactic group achieved significantly higher CC rates than the control group (74.9% vs. 37.8%, p < 0.001). Multivariate logistic regression confirmed that prophylactic metoclopramide was independently associated with higher odds of achieving CC (adjusted OR = 0.20, 95% CI: 0.10–0.40; p < 0.001). Similar improvements were observed for nausea and vomiting control. Subgroup analyses demonstrated consistent benefits across age and sex groups, with particularly notable effects in patients with gastrointestinal cancers.
Conclusions:
Prophylactic metoclopramide significantly improves OINV control in opioid-naïve patients with cancer-related pain during the initiation of strong opioids. These findings support the rational use of early antiemetic prophylaxis in routine clinical practice. Prospective randomized trials are warranted to validate these real-world results and assess long-term safety.
DOI: https://doi.org/10.37349/eds.2026.1008148
Aim:
To design, synthesize, and test small molecules and fragment-based compounds with putative selective anti-mycobacterial activity.
Methods:
Standard chemosynthetic processes were used to synthesize 42 compounds. A cell-based phenotypic screen for inhibitors of mycobacterial growth was used to identify several fragments and small molecules as representatives of urea-, carbamothioate-, and α,β-unsaturated systems (Michael acceptors) chemotypes.
Results:
All 42 compounds exhibited selective toxicity for mycobacteria as demonstrated by their lack of activity against various Gram-positive and Gram-negative bacteria and acid-fast Corynebacterium glutamicum. A thiadiazole compound, similar to (3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)thio)pyrazine-2-carbonitrile), which activates the human lecitin: cholesterol acyltransferase (LCAT), exhibits growth-inhibitory activity [0.6 μg/mL in bovine serum albumin (BSA)-free media] against drug-susceptible Mycobacterium tuberculosis (Mtb). From the urea class, a 1,2,4-triazole-containing urea demonstrated anti-Mtb activity (4.7 μg/mL in BSA-free media). Several carbamothioate-based fragments demonstrated activity against Mycobacterium marinum [with a best minimum inhibitory concentration (MIC) of 6.25 μg/mL in minimal BSA-free media].
Conclusions:
This foundational study demonstrates the utility of these newly designed and synthesized low molecular-weight compounds and fragments as potential antimycobacterials.
Aim:
To design, synthesize, and test small molecules and fragment-based compounds with putative selective anti-mycobacterial activity.
Methods:
Standard chemosynthetic processes were used to synthesize 42 compounds. A cell-based phenotypic screen for inhibitors of mycobacterial growth was used to identify several fragments and small molecules as representatives of urea-, carbamothioate-, and α,β-unsaturated systems (Michael acceptors) chemotypes.
Results:
All 42 compounds exhibited selective toxicity for mycobacteria as demonstrated by their lack of activity against various Gram-positive and Gram-negative bacteria and acid-fast Corynebacterium glutamicum. A thiadiazole compound, similar to (3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)thio)pyrazine-2-carbonitrile), which activates the human lecitin: cholesterol acyltransferase (LCAT), exhibits growth-inhibitory activity [0.6 μg/mL in bovine serum albumin (BSA)-free media] against drug-susceptible Mycobacterium tuberculosis (Mtb). From the urea class, a 1,2,4-triazole-containing urea demonstrated anti-Mtb activity (4.7 μg/mL in BSA-free media). Several carbamothioate-based fragments demonstrated activity against Mycobacterium marinum [with a best minimum inhibitory concentration (MIC) of 6.25 μg/mL in minimal BSA-free media].
Conclusions:
This foundational study demonstrates the utility of these newly designed and synthesized low molecular-weight compounds and fragments as potential antimycobacterials.
DOI: https://doi.org/10.37349/eds.2026.1008145
This article belongs to the special issue Discovery and development of new antibacterial compounds
Over the past several decades there has been a growing recognition of the role that covalent drug candidates have played in the drug development process. With this recognition, compounds that are capable of selectively and irreversibly inactivating their targets through covalent bond formation are now being specifically designed rather than being serendipitously identified. Until recently, vinyl sulfones comprised only a small fraction of the warheads under development as covalent drug candidates, but an increasing number of compounds containing this versatile functional group are now under development and consideration as drug candidates. Vinyl sulfones are generally more reactive than structurally-related acrylamides and vinyl sulfonamides, presenting a challenge for producing target-specific inactivators. The most progress in overcoming this challenge has been made in designing vinyl sulfones as selective inactivators of microbial and human cysteine proteases, incorporating these reactive warheads into peptide and peptide mimetic structures that utilize the substrate recognition motifs of these proteases. However, effective vinyl sulfones have also been produced against a growing range of phosphoryl-utilizing enzymes including kinases, phosphatases and metabolic enzymes. Here, target selection takes advantage of the capability of the sulfonyl group to act as a phosphoryl mimic. An example of this approach is presented for the targeting of a metabolic enzyme, fungal aspartate semialdehyde dehydrogenase, an essential microbial enzyme in amino acid metabolism. The studies conducted to date demonstrate the potential utility of designing vinyl sulfone drug candidates to achieve selectivity against challenging and new drug-resistant targets.
Over the past several decades there has been a growing recognition of the role that covalent drug candidates have played in the drug development process. With this recognition, compounds that are capable of selectively and irreversibly inactivating their targets through covalent bond formation are now being specifically designed rather than being serendipitously identified. Until recently, vinyl sulfones comprised only a small fraction of the warheads under development as covalent drug candidates, but an increasing number of compounds containing this versatile functional group are now under development and consideration as drug candidates. Vinyl sulfones are generally more reactive than structurally-related acrylamides and vinyl sulfonamides, presenting a challenge for producing target-specific inactivators. The most progress in overcoming this challenge has been made in designing vinyl sulfones as selective inactivators of microbial and human cysteine proteases, incorporating these reactive warheads into peptide and peptide mimetic structures that utilize the substrate recognition motifs of these proteases. However, effective vinyl sulfones have also been produced against a growing range of phosphoryl-utilizing enzymes including kinases, phosphatases and metabolic enzymes. Here, target selection takes advantage of the capability of the sulfonyl group to act as a phosphoryl mimic. An example of this approach is presented for the targeting of a metabolic enzyme, fungal aspartate semialdehyde dehydrogenase, an essential microbial enzyme in amino acid metabolism. The studies conducted to date demonstrate the potential utility of designing vinyl sulfone drug candidates to achieve selectivity against challenging and new drug-resistant targets.
DOI: https://doi.org/10.37349/eds.2026.1008147
This article belongs to the special issue The Rise of Targeted Covalent Inhibitors in Drug Discovery
Type 2 diabetes mellitus (T2DM) is a global health challenge often complicated by poor treatment adherence, suboptimal lifestyle habits, and progressive metabolic deterioration. Cognitive behavioral therapy (CBT) has been shown to improve adherence and psychological outcomes, yet its integration with structured lifestyle modification and pharmacotherapy in routine clinical care remains underexplored. A descriptive case series of five patients with uncontrolled T2DM (baseline HbA1c 11–14.5%) was conducted in a primary care setting in Palestine. The intervention combined CBT-inspired behavioral counseling (goal setting, problem-solving, cognitive restructuring) with a structured two-meal low-carbohydrate diet, exercise and sleep hygiene guidance, and pharmacotherapy optimization (withdrawal of insulin/sulfonylureas, initiation of metformin, DPP-4 inhibitors, and SGLT2 inhibitors as appropriate). Patients were followed for 3–6 months. All five patients achieved clinically meaningful improvements. Mean HbA1c decreased from 12.6% at baseline to 7.4% at follow-up. Weight loss ranged from 5–17 kg (mean ~10 kg). Additional benefits included reductions in blood pressure, improvements in renal function and lipid profiles, and resolution of quality-of-life issues such as fatigue and erectile dysfunction. Several patients discontinued insulin or sulfonylurea therapy while maintaining improved glycemic control. The integration of CBT-inspired counseling with structured lifestyle intervention and pharmacotherapy adjustments was associated with short-term improvements in uncontrolled T2DM, including outcomes approaching remission. Although the small sample size and uncontrolled design limit causal interpretation, the program is being done in a low-income, limited-resources area like Palestine. Patients do not have the privilege to attend and receive care from several healthcare professionals. Hence, conducting such practice in a primary care clinic and yielding such results and improvement in diabetes status is promising and provides hope to the patients with low income.
Type 2 diabetes mellitus (T2DM) is a global health challenge often complicated by poor treatment adherence, suboptimal lifestyle habits, and progressive metabolic deterioration. Cognitive behavioral therapy (CBT) has been shown to improve adherence and psychological outcomes, yet its integration with structured lifestyle modification and pharmacotherapy in routine clinical care remains underexplored. A descriptive case series of five patients with uncontrolled T2DM (baseline HbA1c 11–14.5%) was conducted in a primary care setting in Palestine. The intervention combined CBT-inspired behavioral counseling (goal setting, problem-solving, cognitive restructuring) with a structured two-meal low-carbohydrate diet, exercise and sleep hygiene guidance, and pharmacotherapy optimization (withdrawal of insulin/sulfonylureas, initiation of metformin, DPP-4 inhibitors, and SGLT2 inhibitors as appropriate). Patients were followed for 3–6 months. All five patients achieved clinically meaningful improvements. Mean HbA1c decreased from 12.6% at baseline to 7.4% at follow-up. Weight loss ranged from 5–17 kg (mean ~10 kg). Additional benefits included reductions in blood pressure, improvements in renal function and lipid profiles, and resolution of quality-of-life issues such as fatigue and erectile dysfunction. Several patients discontinued insulin or sulfonylurea therapy while maintaining improved glycemic control. The integration of CBT-inspired counseling with structured lifestyle intervention and pharmacotherapy adjustments was associated with short-term improvements in uncontrolled T2DM, including outcomes approaching remission. Although the small sample size and uncontrolled design limit causal interpretation, the program is being done in a low-income, limited-resources area like Palestine. Patients do not have the privilege to attend and receive care from several healthcare professionals. Hence, conducting such practice in a primary care clinic and yielding such results and improvement in diabetes status is promising and provides hope to the patients with low income.
DOI: https://doi.org/10.37349/eds.2026.1008146
Background:
Antimicrobial resistance (AMR) among Gram-positive bacteria has emerged as a significant global health threat, with pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) exhibiting increasing resistance to conventional antibiotics. This systematic review evaluates new advances in nanomaterial-based antimicrobial agents as innovative solutions to combat AMR in Gram-positive bacteria.
Methods:
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies published between 2014 and 2024 were systematically screened and analysed from databases including PubMed, Scopus, Google Scholar, and HINARI. From an initial 1,405 articles, 131 experimental studies that met the inclusion criteria were systematically analysed to harness the advances in nanomaterial-based antimicrobial agents in combating AMR in Gram-positive bacteria.
Results:
The included studies demonstrated that various nanomaterials, including silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), zinc oxide nanoparticles (ZnO NPs), copper and copper oxide nanoparticles (Cu/CuO NPs), as well as polymeric and hybrid systems, exhibited potent antibacterial and antibiofilm activities. Key mechanisms of action included bacterial membrane disruption, reactive oxygen species (ROS) generation, intracellular interference, and targeted drug delivery. Many nanomaterials showed enhanced efficacy and synergistic effects when combined with conventional antibiotics, effectively reducing bacterial load and inhibiting biofilm formation in resistant strains like MRSA.
Discussion:
Nanomaterials offer a multifaceted approach to overcome the evolving resistance mechanisms in Gram-positive pathogens, showing significant preclinical and clinical success. Despite these substantial preclinical results, challenges such as cytotoxicity, environmental impact, scalability, and the potential for resistance adaptation remain unaddressed. Furthermore, important translational barriers persist, most notably insufficient pharmacokinetic data and unclear regulatory pathways. Future efforts must focus on standardized manufacturing, comprehensive toxicity studies, and robust clinical trials to bridge the gap between laboratory innovation and practical therapeutic application.
Background:
Antimicrobial resistance (AMR) among Gram-positive bacteria has emerged as a significant global health threat, with pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) exhibiting increasing resistance to conventional antibiotics. This systematic review evaluates new advances in nanomaterial-based antimicrobial agents as innovative solutions to combat AMR in Gram-positive bacteria.
Methods:
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies published between 2014 and 2024 were systematically screened and analysed from databases including PubMed, Scopus, Google Scholar, and HINARI. From an initial 1,405 articles, 131 experimental studies that met the inclusion criteria were systematically analysed to harness the advances in nanomaterial-based antimicrobial agents in combating AMR in Gram-positive bacteria.
Results:
The included studies demonstrated that various nanomaterials, including silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), zinc oxide nanoparticles (ZnO NPs), copper and copper oxide nanoparticles (Cu/CuO NPs), as well as polymeric and hybrid systems, exhibited potent antibacterial and antibiofilm activities. Key mechanisms of action included bacterial membrane disruption, reactive oxygen species (ROS) generation, intracellular interference, and targeted drug delivery. Many nanomaterials showed enhanced efficacy and synergistic effects when combined with conventional antibiotics, effectively reducing bacterial load and inhibiting biofilm formation in resistant strains like MRSA.
Discussion:
Nanomaterials offer a multifaceted approach to overcome the evolving resistance mechanisms in Gram-positive pathogens, showing significant preclinical and clinical success. Despite these substantial preclinical results, challenges such as cytotoxicity, environmental impact, scalability, and the potential for resistance adaptation remain unaddressed. Furthermore, important translational barriers persist, most notably insufficient pharmacokinetic data and unclear regulatory pathways. Future efforts must focus on standardized manufacturing, comprehensive toxicity studies, and robust clinical trials to bridge the gap between laboratory innovation and practical therapeutic application.
DOI: https://doi.org/10.37349/eds.2026.1008144
Background:
Vascular aging is a major driver of cardiovascular, metabolic, and degenerative diseases, characterized by oxidative stress, mitochondrial dysfunction, endothelial senescence, and impaired proteostasis. Emerging data show that anti-infective drugs can influence these aging pathways beyond antimicrobial activity. However, their capacity to accelerate or slow vascular ageing has not been clearly defined. This review summarizes current evidence on how anti-infective agents modulate vascular ageing mechanisms.
Methods:
A systematic review was conducted following PRISMA 2020 guidelines. Studies from 2000 to 2024 were searched in major indexed databases. Eligible studies included in vitro, animal, and human research evaluating the effects of anti-infective agents on endothelial function, vascular senescence markers (p16INK4a, p21, SA-β-gal), oxidative stress, mitochondrial activity, inflammation, or proteostasis, key determinants of vascular ageing. Studies lacking mechanistic aging endpoints were excluded. Extracted data included drug class, model type, study design, and age-related outcomes. Risk of bias was assessed using SYRCLE, RoB-2, ROBINS-I, and narrative appraisal for in vitro studies.
Results:
Ninety-eight studies were identified; after removing six duplicates, ninety-two met the criteria. Macrolides, tetracyclines, and selected antivirals exerted anti-ageing effects by suppressing senescence-associated secretory phenotype (SASP), preserving mitochondrial integrity, reducing oxidative stress, and enhancing autophagy. Aminoglycosides and fluoroquinolones accelerated vascular ageing by generating reactive oxygen species, inducing DNA damage, and disrupting proteostasis. Antiviral protease inhibitors worsened endothelial dysfunction and metabolic aging. Antifungals such as itraconazole and amphotericin B impaired mitochondrial activity and angiogenesis, contributing to ageing phenotypes. Antiparasitic drugs showed mixed aging outcomes: chloroquine promoted autophagy and longevity, whereas thiabendazole impaired vascular stability. Broad-spectrum antibiotics disrupted the gut-vascular axis, increasing trimethylamine N-oxide, a mediator of inflammatory vascular aging.
Discussion:
Anti-infective drugs display diverse, class-specific effects on vascular aging. Recognizing these age-related actions is essential for safer prescribing and for repurposing anti-infective agents to target pathological vascular aging mechanisms.
Background:
Vascular aging is a major driver of cardiovascular, metabolic, and degenerative diseases, characterized by oxidative stress, mitochondrial dysfunction, endothelial senescence, and impaired proteostasis. Emerging data show that anti-infective drugs can influence these aging pathways beyond antimicrobial activity. However, their capacity to accelerate or slow vascular ageing has not been clearly defined. This review summarizes current evidence on how anti-infective agents modulate vascular ageing mechanisms.
Methods:
A systematic review was conducted following PRISMA 2020 guidelines. Studies from 2000 to 2024 were searched in major indexed databases. Eligible studies included in vitro, animal, and human research evaluating the effects of anti-infective agents on endothelial function, vascular senescence markers (p16INK4a, p21, SA-β-gal), oxidative stress, mitochondrial activity, inflammation, or proteostasis, key determinants of vascular ageing. Studies lacking mechanistic aging endpoints were excluded. Extracted data included drug class, model type, study design, and age-related outcomes. Risk of bias was assessed using SYRCLE, RoB-2, ROBINS-I, and narrative appraisal for in vitro studies.
Results:
Ninety-eight studies were identified; after removing six duplicates, ninety-two met the criteria. Macrolides, tetracyclines, and selected antivirals exerted anti-ageing effects by suppressing senescence-associated secretory phenotype (SASP), preserving mitochondrial integrity, reducing oxidative stress, and enhancing autophagy. Aminoglycosides and fluoroquinolones accelerated vascular ageing by generating reactive oxygen species, inducing DNA damage, and disrupting proteostasis. Antiviral protease inhibitors worsened endothelial dysfunction and metabolic aging. Antifungals such as itraconazole and amphotericin B impaired mitochondrial activity and angiogenesis, contributing to ageing phenotypes. Antiparasitic drugs showed mixed aging outcomes: chloroquine promoted autophagy and longevity, whereas thiabendazole impaired vascular stability. Broad-spectrum antibiotics disrupted the gut-vascular axis, increasing trimethylamine N-oxide, a mediator of inflammatory vascular aging.
Discussion:
Anti-infective drugs display diverse, class-specific effects on vascular aging. Recognizing these age-related actions is essential for safer prescribing and for repurposing anti-infective agents to target pathological vascular aging mechanisms.
DOI: https://doi.org/10.37349/eds.2026.1008143
DOI: https://doi.org/10.37349/eds.2026.1008142
Aim:
The prevalence of multidrug-resistant “superbugs”, particularly Acinetobacter baumannii and Klebsiella pneumoniae, is a menacing phenomenon in society, rendering last-resort antibiotics increasingly suboptimal and ineffective. Carbapenemase enzymes play a major role in this resistance by hydrolysing carbapenem antibiotics. This study aims to identify and characterize potential non-covalent carbapenemase inhibitors using multiscale computational approaches.
Methods:
A focused library of 245 compounds, comprising pharmacopeial derivatives and chemogenomic molecules, was screened using a hierarchical virtual screening workflow. Top-ranked hits were further evaluated by rescoring for thermodynamic affinity. The most promising candidate was subjected to a 100 ns molecular dynamics (MD) simulation to assess binding stability, followed by Well-Tempered Metadynamics (WTMetaD) to characterise the free energy landscape and binding behaviour. Pharmacokinetic and toxicity profiles were predicted using SwissADME and ProTox 3.0.
Results:
Three compounds, daunorubicin, doxorubicin, and EUB0000226b, emerged as potential carbapenemase inhibitors. EUB0000226b demonstrated the most favourable binding affinity and structural novelty. MD simulations showed protein stability, while ligand RMSD fluctuations (2.4–5.6 Å) suggested flexible binding. WTMetaD analysis revealed a solvent-separated metastable state that increased ligand residence time within the active site. ADME and toxicity predictions indicated acceptable drug-likeness, good gastrointestinal absorption, and a generally safe profile.
Conclusions:
Multiscale computational analysis identified EUB0000226b as a promising non-covalent carbapenemase inhibitor with favourable binding energetics, dynamic stability, and drug-like properties. These findings support its further experimental validation and potential development for combating carbapenem-resistant bacterial pathogens.
Aim:
The prevalence of multidrug-resistant “superbugs”, particularly Acinetobacter baumannii and Klebsiella pneumoniae, is a menacing phenomenon in society, rendering last-resort antibiotics increasingly suboptimal and ineffective. Carbapenemase enzymes play a major role in this resistance by hydrolysing carbapenem antibiotics. This study aims to identify and characterize potential non-covalent carbapenemase inhibitors using multiscale computational approaches.
Methods:
A focused library of 245 compounds, comprising pharmacopeial derivatives and chemogenomic molecules, was screened using a hierarchical virtual screening workflow. Top-ranked hits were further evaluated by rescoring for thermodynamic affinity. The most promising candidate was subjected to a 100 ns molecular dynamics (MD) simulation to assess binding stability, followed by Well-Tempered Metadynamics (WTMetaD) to characterise the free energy landscape and binding behaviour. Pharmacokinetic and toxicity profiles were predicted using SwissADME and ProTox 3.0.
Results:
Three compounds, daunorubicin, doxorubicin, and EUB0000226b, emerged as potential carbapenemase inhibitors. EUB0000226b demonstrated the most favourable binding affinity and structural novelty. MD simulations showed protein stability, while ligand RMSD fluctuations (2.4–5.6 Å) suggested flexible binding. WTMetaD analysis revealed a solvent-separated metastable state that increased ligand residence time within the active site. ADME and toxicity predictions indicated acceptable drug-likeness, good gastrointestinal absorption, and a generally safe profile.
Conclusions:
Multiscale computational analysis identified EUB0000226b as a promising non-covalent carbapenemase inhibitor with favourable binding energetics, dynamic stability, and drug-like properties. These findings support its further experimental validation and potential development for combating carbapenem-resistant bacterial pathogens.
DOI: https://doi.org/10.37349/eds.2026.1008140
This article belongs to the special issue Discovery and development of new antibacterial compounds
Immunotherapy has transformed oncology, yet has only been marginally effective in prostate cancer (PCa), which is a malignancy with a low mutational load and a highly immunosuppressive tumor microenvironment (TME). This critical review is a reflection on the changing position of the innovative immunotherapies in PCa that extends beyond the description stage to synthesize the synergies and constraints of immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, and next-generation modalities such as bispecific T-cell engagers (BiTEs). We assess the mechanistic reasoning of combination therapies, comprising androgen receptor signaling communicators, PARP communicators, and radioligand therapies, which seek to modulate the immunogenicity of the immune-cold PCa TME. Also, we combine new knowledge to novel resistance pathways, including the newly discovered thrombospondin-1-CD47 axis, in the process of T cell exhaustion through calcineurin-NFAT signaling. Although some preclinical data and initial clinical indicators in biomarker-selected subpopulations are promising, the vast majority of Phase III trials of ICIs in unselected populations with metastatic castration-resistant prostate cancer (mCRPC) have failed. This review reveals that the next generation of PCa immunotherapy would not be sequential monotherapies but rather rationally designed multimodal combinations guided by profound molecular and immune profiling to overcome inherent resistance mechanisms.
Immunotherapy has transformed oncology, yet has only been marginally effective in prostate cancer (PCa), which is a malignancy with a low mutational load and a highly immunosuppressive tumor microenvironment (TME). This critical review is a reflection on the changing position of the innovative immunotherapies in PCa that extends beyond the description stage to synthesize the synergies and constraints of immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, and next-generation modalities such as bispecific T-cell engagers (BiTEs). We assess the mechanistic reasoning of combination therapies, comprising androgen receptor signaling communicators, PARP communicators, and radioligand therapies, which seek to modulate the immunogenicity of the immune-cold PCa TME. Also, we combine new knowledge to novel resistance pathways, including the newly discovered thrombospondin-1-CD47 axis, in the process of T cell exhaustion through calcineurin-NFAT signaling. Although some preclinical data and initial clinical indicators in biomarker-selected subpopulations are promising, the vast majority of Phase III trials of ICIs in unselected populations with metastatic castration-resistant prostate cancer (mCRPC) have failed. This review reveals that the next generation of PCa immunotherapy would not be sequential monotherapies but rather rationally designed multimodal combinations guided by profound molecular and immune profiling to overcome inherent resistance mechanisms.
DOI: https://doi.org/10.37349/eds.2026.1008141
