Exploration of Drug Science

No.	Parameter	Descriptors
1	Formation energy	–1,178.43 au
2	Dipole moment	9.00 Debye
3	E_HOMO	–5.5427 eV
4	E_LUMO	–1.1848 eV
5	Energy gap (ΔE)	4.3579 eV
6	Electronegativity (χ)	3.3638 eV
7	Chemical hardness (η)	2.1790 eV
8	Chemical potential (μ)	–3.3638 eV
9	Electrophilicity (ω)	2.5960 eV
10	Softness (S)	0.2295 eV^–1

Supplementary materials

The supplementary tables for this article are available at: https://www.explorationpub.com/uploads/Article/file/1008140_sup_1.xlsx and https://www.explorationpub.com/uploads/Article/file/1008140_sup_2.xlsx. The supplementary movie for this article is available at: https://www.explorationpub.com/uploads/Article/file/1008140_sup_1.mp4.

Declarations

Author contributions

AOM: Conceptualization, Data curation, Formal analysis, Methodology, Resources, Investigation, Writing—original draft. AJA: Formal analysis, Methodology, Investigation, Writing—review & editing. MEA: Resources, Methodology, Investigation, Writing—review & editing. SOI: Visualization, Resources, Writing—review & editing. YOA: Software, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Authors declare no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Data generated from this study are available from the corresponding author upon reasonable request.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Nikaido H. Multidrug resistance in bacteria. Annu Rev Biochem. 2009;78:119–46. [DOI] [PubMed] [PMC]

Bedawy A, Ramadan R, Elharrisi M, Elarini HM. In vitro activity of ceftazidime-avibactam in combination with aztreonam against carbapenem-resistant Enterobacterales isolated from intensive care units. Microbe Infect Dis. 2024;5:1519–29. [DOI]

Bradley G, Juranka PF, Ling V. Mechanism of multidrug resistance. Biochim Biophys Acta. 1988;948:87–128. [DOI] [PubMed]

Grimsey EM, Weston N, Ricci V, Stone JW, Piddock LJV. Overexpression of RamA, Which Regulates Production of the Multidrug Resistance Efflux Pump AcrAB-TolC, Increases Mutation Rate and Influences Drug Resistance Phenotype. Antimicrob Agents Chemother. 2020;64:e02460–19. [DOI] [PubMed] [PMC]

Mohanty H, Pachpute S, Yadav RP. Mechanism of drug resistance in bacteria: efflux pump modulation for designing of new antibiotic enhancers. Folia Microbiol (Praha). 2021;66:727–39. [DOI] [PubMed]

Saravanakumar A, Sadighi A, Ryu R, Akhlaghi F. Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016. Clin Pharmacokinet. 2019;58:1281–94. [DOI] [PubMed] [PMC]

Frost I, Sati H, Garcia-Vello P, Hasso-Agopsowicz M, Lienhardt C, Gigante V, et al. The role of bacterial vaccines in the fight against antimicrobial resistance: an analysis of the preclinical and clinical development pipeline. Lancet Microbe. 2023;4:e113–25. [DOI] [PubMed] [PMC]

Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al.; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18:318–27. [DOI] [PubMed]

WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance [Internet]. Geneva: WHO; c2025 [cited 2025 May 20]. Available from: https://www.who.int/publications/i/item/9789240093461

10.

Parmanik A, Das S, Kar B, Bose A, Dwivedi GR, Pandey MM. Current Treatment Strategies Against Multidrug-Resistant Bacteria: A Review. Curr Microbiol. 2022;79:388. [DOI] [PubMed] [PMC]

11.

Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015;40:277–83. [PubMed] [PMC]

12.

Tahmasebi H, Arjmand N, Monemi M, Babaeizad A, Alibabaei F, Alibabaei N, et al. From Cure to Crisis: Understanding the Evolution of Antibiotic-Resistant Bacteria in Human Microbiota. Biomolecules. 2025;15:93. [DOI] [PubMed] [PMC]

13.

Elshobary ME, Badawy NK, Ashraf Y, Zatioun AA, Masriya HH, Ammar MM, et al. Combating Antibiotic Resistance: Mechanisms, Multidrug-Resistant Pathogens, and Novel Therapeutic Approaches: An Updated Review. Pharmaceuticals (Basel). 2025;18:402. [DOI] [PubMed] [PMC]

14.

Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med. 2016;6:a025247. [DOI] [PubMed] [PMC]

15.

Galgano M, Pellegrini F, Catalano E, Capozzi L, Del Sambro L, Sposato A, et al. Acquired Bacterial Resistance to Antibiotics and Resistance Genes: From Past to Future. Antibiotics (Basel). 2025;14:222. [DOI] [PubMed] [PMC]

16.

Blázquez J, Rodríguez-Beltrán J, Matic I. Antibiotic-Induced Genetic Variation: How It Arises and How It Can Be Prevented. Annu Rev Microbiol. 2018;72:209–30. [DOI] [PubMed]

17.

Wang X, Yu D, Chen L. Antimicrobial resistance and mechanisms of epigenetic regulation. Front Cell Infect Microbiol. 2023;13:1199646. [DOI] [PubMed] [PMC]

18.

Coates ARM, Hu Y, Holt J, Yeh P. Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. Expert Rev Anti Infect Ther. 2020;18:5–15. [DOI] [PubMed]

19.

Wang N, Luo J, Deng F, Huang Y, Zhou H. Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance to Aminoglycoside Antibiotics. Front Pharmacol. 2022;13:839808. [DOI] [PubMed] [PMC]

20.

Touati A, Ibrahim NA, Idres T. Disarming Staphylococcus aureus: Review of Strategies Combating This Resilient Pathogen by Targeting Its Virulence. Pathogens. 2025;14:386. [DOI] [PubMed] [PMC]

21.

Ibrahim S, Al-Saryi N, Al-Kadmy IMS, Aziz SN. Multidrug-resistant Acinetobacter baumannii as an emerging concern in hospitals. Mol Biol Rep. 2021;48:6987–98. [DOI] [PubMed] [PMC]

22.

Alali WQ, AlFouzan W, Dhar R. Prevalence of antimicrobial resistance in Gram-negative clinical isolates from a major secondary hospital in Kuwait: a retrospective descriptive study. Germs. 2021;11:498–511. [DOI] [PubMed] [PMC]

23.

Shi T, Xie L. Distribution and antimicrobial resistance analysis of gram-negative bacilli isolated from a tertiary hospital in Central China: a 10-year retrospective study from 2012 to 2021. Front Microbiol. 2023;14:1297528. [DOI] [PubMed] [PMC]

24.

Verma P, Tiwari M, Tiwari V. Efflux pumps in multidrug-resistant Acinetobacter baumannii: Current status and challenges in the discovery of efflux pumps inhibitors. Microb Pathog. 2021;152:104766. [DOI] [PubMed]

25.

Abd-ElNasser R, Abdel-Rahim MH, Mahmoud MA, Elkhawaga A, Hassnein K. Antibiotic resistance of Acinetobacter baumannii: An urgent need for new therapy and infection control. B Pharm Sci Assiut Univ. 2020;43:265–79. [DOI]

26.

Foglia F, Ambrosino A, Bashir S, Finamore E, Zannella C, Donnarumma G, et al. Prevalence of Acinetobacter baumannii Multidrug Resistance in University Hospital Environment. Antibiotics (Basel). 2025;14:490. [DOI] [PubMed] [PMC]

27.

Müller C, Reuter S, Wille J, Xanthopoulou K, Stefanik D, Grundmann H, et al. A global view on carbapenem-resistant Acinetobacter baumannii. mBio. 2023;14:e0226023. [DOI] [PubMed] [PMC]

28.

Mohd Sazlly Lim S, Zainal Abidin A, Liew SM, Roberts JA, Sime FB. The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis. J Infect. 2019;79:593–600. [DOI] [PubMed]

29.

Teklu DS, Negeri AA, Legese MH, Bedada TL, Woldemariam HK, Tullu KD. Extended-spectrum beta-lactamase production and multi-drug resistance among Enterobacteriaceae isolated in Addis Ababa, Ethiopia. Antimicrob Resist Infect Control. 2019;8:39. [DOI] [PubMed] [PMC]

30.

Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399:629–55. [DOI] [PubMed] [PMC]

31.

Salawudeen A, Raji YE, Jibo GG, Desa MNM, Neoh HM, Masri SN, et al. Epidemiology of multidrug-resistant Klebsiella pneumoniae infection in clinical setting in South-Eastern Asia: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2023;12:142. [DOI] [PubMed] [PMC]

32.

Wu W, Jin Y, Bai F, Jin S. Pseudomonas aeruginosa. In: Tang YW, Liu D, Sussman M, Poxton I, Schwartzman J, editors. Molecular Medical Microbiology. Academic Press; 2015. pp. 753–67.

33.

Breijyeh Z, Jubeh B, Karaman R. Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It. Molecules. 2020;25:1340. [DOI] [PubMed] [PMC]

34.

Sivarajan K, Ravindhiran R, Sekar JN, Murugesan R, Chidambaram K, Dhandapani K. Deciphering the impact of Acinetobacter baumannii on human health, and exploration of natural compounds as efflux pump inhibitors to treat multidrug resistance. J Med Microbiol. 2024;73. [DOI] [PubMed]

35.

Khalif OI, Alkalifawi EJ. Green-Synthesized Zinc Oxide Nanoparticles for Acinetobacter baumannii Control: A Review of Plant-Based Approaches. Cureus. 2025;17:e83506. [DOI] [PubMed] [PMC]

36.

Bamigboye M, Mustapha A, Danjuma F. Bioactivity Assessment of 8-Hydroxyquinoline and Monosodium Glutamate Mixed Ligand Copper Complex: Experimental and Computational. Univ Thi-Qar J Sci. 2024;11:175–84. [DOI]

37.

Galaxy Community. The Galaxy platform for accessible, reproducible, and collaborative data analyses: 2024 update. Nucleic Acids Res. 2024;52:W83–94. [DOI] [PubMed] [PMC]

38.

Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S, Cattoir V, et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother. 2020;75:3491–500. [DOI] [PubMed] [PMC]

39.

Clausen PTLC, Aarestrup FM, Lund O. Rapid and precise alignment of raw reads against redundant databases with KMA. BMC Bioinformatics. 2018;19:307. [DOI] [PubMed] [PMC]

40.

Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O, Villa L, et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother. 2014;58:3895–903. [DOI] [PubMed] [PMC]

41.

Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, et al. BLAST+: architecture and applications. BMC Bioinformatics. 2009;10:421. [DOI] [PubMed] [PMC]

42.

Lu C, Wu C, Ghoreishi D, Chen W, Wang L, Damm W, et al. OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space. J Chem Theory Comput. 2021;17:4291–300. [DOI] [PubMed]

43.

Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47:1739–49. [DOI] [PubMed]

44.

Lyne PD, Lamb ML, Saeh JC. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem. 2006;49:4805–8. [DOI] [PubMed]

45.

D. E. Shaw Research. Desmond Molecular Dynamics System [software]. New York: Schrödinger, LLC.; 2021.

46.

Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79:926–35. [DOI]

47.

Tiwary P, Parrinello M. A time-independent free energy estimator for metadynamics. J Phys Chem B. 2015;119:736–42. [DOI] [PubMed]

48.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. [DOI] [PubMed] [PMC]

49.

Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024;52:W513–20. [DOI] [PubMed] [PMC]

50.

Frisch MJ, Trucks G, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09 [software]. Wallingford: Gaussian Inc.; 2009.

51.

Becke AD. Density-functional thermochemistry III. J Chem Phys. 1993;98:5648–52.

52.

Lee C, Yang W, Parr R. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988;37:785–9. [DOI] [PubMed]

53.

Tomasi J, Mennucci B, Cammi R. Quantum mechanical continuum solvation models. Chem Rev. 2005;105:2999–3093. [DOI] [PubMed]

54.

Mustapha A, Bamigboye M, Adefunke A, Ayobami L, Ibrahim SO, Mutiat S, et al. Nickel(II) mixed-ligand complex of 8-hydroxyquinoline and MSG. J Mol Struct. 2025;1343:142667. [DOI]

55.

Pearson RG. Absolute electronegativity and hardness: application to inorganic chemistry. Inorg Chem. 1988;27:734–40. [DOI]

56.

Pearson RG. Hard and soft acids and bases—the evolution of a chemical concept. Coord Chem Rev. 1990;100:403–25. [DOI]

57.

Gázquez JL, Cedillo A, Vela A. Electrodonating and electroaccepting powers. J Phys Chem A. 2007;111:1966–70. [DOI] [PubMed]

58.

Touchon M, Cury J, Yoon EJ, Krizova L, Cerqueira GC, Murphy C, et al. The genomic diversification of the whole Acinetobacter genus: origins, mechanisms, and consequences. Genome Biol Evol. 2014;6:2866–82. [DOI] [PubMed] [PMC]

59.

Wyres KL, Holt KE. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Curr Opin Microbiol. 2018;45:131–9. [DOI] [PubMed]

60.

Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, et al. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000;406:959–64. [DOI] [PubMed]

61.

Chan KG, Yin WF, Lim YL. Complete Genome Sequence of Pseudomonas aeruginosa Strain YL84, a Quorum-Sensing Strain Isolated from Compost. Genome Announc. 2014;2:e00246–14. [DOI] [PubMed] [PMC]

62.

National Center for Biotechnology Information. WGS of CR A. baumannii (SRR19723078) [dataset]. 2022 [cited 2025 May 25]. Sequence Read Archive. Available from: https://trace.ncbi.nlm.nih.gov/Traces/sra/?run=SRR19723078

63.

National Center for Biotechnology Information. WGS of Klebsiella pneumoniae: Urine (SRR32133156) [dataset]. 2025 [cited 2025 May 25]. Sequence Read Archive. Available from: https://trace.ncbi.nlm.nih.gov/Traces/sra/?run=SRR32133156

64.

National Center for Biotechnology Information. P. aeruginosa (SRR31701364) [dataset]. 2024 [cited 2025 May 25]. Sequence Read Archive. Available from: https://trace.ncbi.nlm.nih.gov/Traces/sra/?run=SRR31701364

65.

Evans BA, Amyes SGB. OXA β-lactamases. Clin Microbiol Rev. 2014;27:241–63. [DOI] [PubMed] [PMC]

66.

Docquier JD, Mangani S. An update on β-lactamase inhibitor discovery and development. Drug Resist Updat. 2018;36:13–29. [DOI] [PubMed]

67.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2025 update. Nucleic Acids Res. 2025;53:D1516–25. [DOI] [PubMed] [PMC]

68.

Schäfer E, Malecki M, Tellez-Castillo CJ, Pfennigwerth N, Marlinghaus L, Higgins PG, et al. Molecular surveillance of carbapenemase-producing Pseudomonas aeruginosa at three medical centres in Cologne, Germany. Antimicrob Resist Infect Control. 2019;8:208. [DOI] [PubMed] [PMC]

69.

Reyes J, Komarow L, Chen L, Ge L, Hanson BM, Cober E, et al.; Antibacterial Resistance Leadership Group and Multi-Drug Resistant Organism Network Investigators. Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study. Lancet Microbe. 2023;4:e159–70. [DOI] [PubMed] [PMC]

70.

Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr. 1993;26:283–91. [DOI]

71.

Lovell SC, Davis IW, Arendall WB 3rd, de Bakker PI, Word JM, Prisant MG, et al. Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins. 2003;50:437–50. [DOI] [PubMed]

72.

British Pharmacopoeia Commission, editor. British Pharmacopoeia 2024. London: Medicines and Healthcare products Regulatory Agency (MHRA); 2023.

73.

van der Zanden SY, Qiao X, Neefjes J. New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J. 2021;288:6095–111. [DOI] [PubMed] [PMC]

74.

Kciuk M, Gielecińska A, Mujwar S, Kołat D, Kałuzińska-Kołat Ż, Celik I, et al. Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity. Cells. 2023;12:659. [DOI] [PubMed] [PMC]

75.

Hobson CA, Bonacorsi S, Hocquet D, Baruchel A, Fahd M, Storme T, et al. Impact of anticancer chemotherapy on the extension of beta-lactamase spectrum: an example with KPC-type carbapenemase activity towards ceftazidime-avibactam. Sci Rep. 2020;10:589. [DOI] [PubMed] [PMC]

76.

Zhang M, Yang S, Liu Y, Zou Z, Zhang Y, Tian Y, et al. Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens. Int J Antimicrob Agents. 2024;64:107337. [DOI] [PubMed]

77.

Souza PCT, Limongelli V, Wu S, Marrink SJ, Monticelli L. Perspectives on High-Throughput Ligand/Protein Docking With Martini MD Simulations. Front Mol Biosci. 2021;8:657222. [DOI] [PubMed] [PMC]

78.

Guterres H, Im W. Improving Protein-Ligand Docking Results with High-Throughput Molecular Dynamics Simulations. J Chem Inf Model. 2020;60:2189–98. [DOI] [PubMed] [PMC]

79.

Copeland RA. The drug-target residence time model: a 10-year retrospective. Nat Rev Drug Discov. 2016;15:87–95. [DOI] [PubMed]

80.

Liu K, Kokubo H. Exploring the Stability of Ligand Binding Modes to Proteins by Molecular Dynamics Simulations: A Cross-docking Study. J Chem Inf Model. 2017;57:2514–22. [DOI] [PubMed]

81.

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46:W257–63. [DOI] [PubMed] [PMC]

82.

Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res. 2014;42:W53–8. [DOI] [PubMed] [PMC]

83.

Balogun TA, Ipinloju N, Abdullateef OT, Moses SI, Omoboyowa DA, James AC, et al. Computational Evaluation of Bioactive Compounds from Colocasia affinis Schott as a Novel EGFR Inhibitor for Cancer Treatment. Cancer Inform. 2021;20:11769351211049244. [DOI] [PubMed] [PMC]