{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:07:29Z","timestamp":1779426449055,"version":"3.53.1"},"reference-count":84,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The increasing prevalence of antimicrobial resistance and biofilm-associated infections has intensified the search for alternative anti-infective strategies. Short peptide-based molecules have attracted growing interest due to their structural simplicity, biocompatibility, and multifunctional biological properties. In this study, the antimicrobial and antibiofilm activities of two dipeptides, glycyl\u2013histidine and methionyl\u2013glycine, were evaluated against reference microorganisms, including Escherichia coli ATCC 35218, Klebsiella pneumoniae MTCC 109, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and Candida albicans ATCC 10231. Antimicrobial activity was determined using broth microdilution and disk diffusion assays, while antibiofilm effects were evaluated at sub-inhibitory concentrations using a crystal violet-based biofilm inhibition assay supported by light microscopy. In addition, the electronic structure, binding interactions, and pharmacokinetic properties of the dipeptides were investigated using integrated density functional theory (DFT), molecular docking, and ADME analyses. Glycyl\u2013histidine exhibited antimicrobial activity against all tested bacterial strains (MIC: 12.5 mg\/mL) and against C. albicans (MIC: 50 mg\/mL), whereas methionyl\u2013glycine showed no detectable antimicrobial activity. Both dipeptides demonstrated microorganism-dependent antibiofilm effects, with glycyl\u2013histidine consistently displaying stronger activity. Notably, glycyl\u2013histidine reduced biofilm formation by up to 88% in K. pneumoniae and by 54% in P. aeruginosa at 0.5 \u00d7 MIC. In C. albicans, biofilm formation decreased by 22\u201339% under conditions where the reference antibiotic solution showed no antibiofilm effect. Computational analyses supported the experimental findings and provided molecular-level insights into the antimicrobial and antibiofilm potential of glycyl\u2013histidine. Overall, these results identify glycyl\u2013histidine as a promising anti-infective dipeptide and highlight its potential as a promising building block for the development of novel anti-infective agents.<\/jats:p>","DOI":"10.3390\/molecules31101641","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:46:55Z","timestamp":1778676415000},"page":"1641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimicrobial and Antibiofilm Activities of Glycyl\u2013Histidine and Methionyl\u2013Glycine Dipeptides: In Vitro and Molecular Docking Studies"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5994-1727","authenticated-orcid":false,"given":"Gulcan","family":"Sahal","sequence":"first","affiliation":[{"name":"Department of Biology, Biotechnology Division, Faculty of Science, Hacettepe University, 06800 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-1759","authenticated-orcid":false,"given":"Tu\u011f\u00e7e Deniz","family":"Karaca","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services, Gazi University, 06830 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Sert","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Art & Sciences, Yozgat Bozok University, 66900 Yozgat, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meltem","family":"Maras","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Science Education, Faculty of Eregli Education, Zonguldak B\u00fclent Ecevit University, 67300 Zonguldak, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8907-1344","authenticated-orcid":false,"given":"Alev","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Science Education, Faculty of Gazi Education, Gazi University, 06500 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1016\/j.cell.2024.05.013","article-title":"Discovery of Antimicrobial Peptides in the Global Microbiome with Machine Learning","volume":"187","author":"Torres","year":"2024","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial Biofilms: A Common Cause of Persistent Infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrmicro.2016.94","article-title":"Biofilms: An Emergent Form of Bacterial Life","volume":"14","author":"Flemming","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Moretta, A., Scieuzo, C., Petrone, A.M., Salvia, R., Manniello, M.D., Franco, A., Lucchetti, D., Vassallo, A., Vogel, H., and Sgambato, A. (2021). Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.668632"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Baran, A., Kwiatkowska, A., and Potocki, L. (2023). Antibiotics and Bacterial Resistance\u2014A Short Story of an Endless Arms Race. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065777"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ibisanmi, T.A., Jiang, X., Willcox, M., and Kumar, N. (2026). Recent Advances in Computational Antimicrobial Peptide Discovery through Big Data, Modeling, and Artificial Intelligence and Their Interplay in Ushering the Next Golden Era of Drug Development. Front. Bioinform., 6.","DOI":"10.3389\/fbinf.2026.1749404"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhou, S., Sun, Z., Liu, L., Xi, Y., Zhou, L., Yang, Z., and Zhou, J. (2026). Overcoming Multidrug Resistance: Antimicrobial Peptides as a Next-Generation Therapeutic Strategy. Front. Cell. Infect. Microbiol., 16.","DOI":"10.3389\/fcimb.2026.1745427"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"La Manna, S., Di Natale, C., Florio, D., and Marasco, D. (2018). Peptides as Therapeutic Agents for Inflammatory-Related Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092714"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127822","DOI":"10.1016\/j.micres.2024.127822","article-title":"Antimicrobial Peptides: Opportunities and Challenges in Overcoming Resistance","volume":"286","author":"Bucataru","year":"2024","journal-title":"Microbiol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rodriguez, C.A., Papanastasiou, E.A., Juba, M., and Bishop, B. (2014). Covalent Modification of a Ten-Residue Cationic Antimicrobial Peptide with Levofloxacin. Front. Chem., 2.","DOI":"10.3389\/fchem.2014.00071"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41579-019-0273-7","article-title":"The Mycobacterial Cell Envelope\u2014A Moving Target","volume":"18","author":"Dulberger","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Di Somma, A., Moretta, A., Can\u00e8, C., Cirillo, A., and Duilio, A. (2020). Antimicrobial and Antibiofilm Peptides. Biomolecules, 10.","DOI":"10.3390\/biom10040652"},{"key":"ref_13","first-page":"351","article-title":"Evaluation of Glycyl-Arginine and Lysyl-Aspartic Acid Dipeptides for Their Antimicrobial, Antibiofilm, and Anticancer Potentials","volume":"205","author":"Karaca","year":"2023","journal-title":"Arch. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ezugwu, J.A., Okoro, U.C., Ezeokonkwo, M.A., Bhimapaka, C.R., Okafor, S.N., Ugwu, D.I., Ekoh, O.C., and Attah, S.I. (2020). Novel Leu-Val-Based Dipeptides as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.583926"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2000074","DOI":"10.1002\/ardp.202000074","article-title":"Synthesis and Biological Evaluation of Val\u2013Val Dipeptide\u2013Sulfonamide Conjugates","volume":"353","author":"Ezugwu","year":"2020","journal-title":"Arch. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"133280","DOI":"10.1016\/j.molstruc.2022.133280","article-title":"Pro-Gly-Based Dipeptide Containing Sulphonamide Functionality: Synthesis, Characterization, Antidiabetic, Antioxidant, and Anti-Inflammatory Activities, and Computational Studies","volume":"1264","author":"Attah","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Apostolidou, C.P., Kokotidou, C., Platania, V., Nikolaou, V., Landrou, G., Nikoloudakis, E., Charalambidis, G., Chatzinikolaidou, M., Coutsolelos, A.G., and Mitraki, A. (2024). Antimicrobial Potency of Fmoc-Phe-Phe Dipeptide Hydrogels with Encapsulated Porphyrin Chromophores Is a Promising Alternative in Antimicrobial Resistance. Biomolecules, 14.","DOI":"10.3390\/biom14020226"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tao, M., Sun, A., Shao, H., Ye, H., Yu, G., Chen, D., and Zhang, W. (2025). Heterologous Expression and Antimicrobial Targets of a Novel Glycine-Rich Antimicrobial Peptide from Artemia franciscana. Mar. Drugs, 23.","DOI":"10.3390\/md23080330"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12276","DOI":"10.1074\/jbc.M710338200","article-title":"Identification of a Glycine Motif Required for Packing in EmrE, a Multidrug Transporter from Escherichia coli","volume":"283","author":"Elbaz","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.15671\/hjbc.1464084","article-title":"Antimicrobial, Antibiofilm and Anticancer Potentials of Glycine and Glycyl-Glycine: An In Vitro Study","volume":"52","author":"Sahal","year":"2024","journal-title":"Hacet. J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7799","DOI":"10.1021\/jp411901m","article-title":"2D IR Spectroscopy of Histidine: Probing Side-Chain Structure and Dynamics via Backbone Amide Vibrations","volume":"118","author":"Ghosh","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1752-153X-7-44","article-title":"The Multiple Roles of Histidine in Protein Interactions","volume":"7","author":"Liao","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.1093\/jn\/136.6.1636S","article-title":"The Sulfur-Containing Amino Acids: An Overview","volume":"136","author":"Brosnan","year":"2006","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1096\/fj.08-118414","article-title":"Methionine in Proteins Defends against Oxidative Stress","volume":"23","author":"Luo","year":"2009","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100644","DOI":"10.1016\/j.mtbio.2023.100644","article-title":"Self-Assembled Short Peptides: Recent Advances and Strategies for Potential Pharmaceutical Applications","volume":"20","author":"Yang","year":"2023","journal-title":"Mater. Today Bio"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.bbamem.2012.11.017","article-title":"Selective Antimicrobial Activity and Mode of Action of Adepantins, Glycine-Rich Peptide Antibiotics Based on Anuran Antimicrobial Peptide Sequences","volume":"1828","author":"Guida","year":"2013","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mahlapuu, M., H\u00e5kansson, J., Ringstad, L., and Bj\u00f6rn, C. (2016). Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00194"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1016\/S1473-3099(20)30327-3","article-title":"The Value of Antimicrobial Peptides in the Age of Resistance","volume":"20","author":"Magana","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"FUNK-0035-2016","DOI":"10.1128\/microbiolspec.FUNK-0035-2016","article-title":"The Fungal Cell Wall: Structure, Biosynthesis, and Function","volume":"5","author":"Gow","year":"2017","journal-title":"Microbiol. Spectr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0966-842X(03)00117-3","article-title":"Antifungal Agents: Mechanisms of Action","volume":"11","author":"Odds","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial Peptides: Pore Formers or Metabolic Inhibitors in Bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kim, S.H., Min, Y.-H., and Park, M.C. (2025). Antimicrobial Peptides: Current Status, Mechanisms of Action, and Strategies to Overcome Therapeutic Limitations. Microorganisms, 13.","DOI":"10.3390\/microorganisms13112574"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, H., Lv, J., Ma, Z., Ma, J., and Chen, J. (2025). Advances in Antimicrobial Peptides: Mechanisms, Design Innovations, and Biomedical Potential. Molecules, 30.","DOI":"10.3390\/molecules30071529"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial Biofilms: From the Natural Environment to Infectious Diseases","volume":"2","author":"Costerton","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.micro.57.030502.090720","article-title":"Bacterial Biofilms: An Emerging Link to Disease Pathogenesis","volume":"57","author":"Parsek","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3390\/pathogens3030743","article-title":"Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae","volume":"3","author":"Vuotto","year":"2014","journal-title":"Pathogens"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","article-title":"Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors","volume":"11","author":"Podschun","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Martin, R.M., and Bachman, M.A. (2018). Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00004"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3201\/eid0702.010226","article-title":"Biofilms and Device-Associated Infections","volume":"7","author":"Donlan","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/ja.2012.101","article-title":"Susceptibility of Different Phases of Biofilm of Klebsiella pneumoniae to Three Different Antibiotics","volume":"66","author":"Singla","year":"2013","journal-title":"J. Antibiot."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20983","DOI":"10.3390\/ijms141020983","article-title":"Biofilm Matrix and Its Regulation in Pseudomonas aeruginosa","volume":"14","author":"Wei","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Balducci, E., Papi, F., Capialbi, D.E., and Del Bino, L. (2023). Polysaccharides\u2019 Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044030"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ball\u00e9n, V., Cepas, V., Ratia, C., Gabasa, Y., and Soto, S.M. (2022). Clinical Escherichia coli: From Biofilm Formation to New Antibiofilm Strategies. Microorganisms, 10.","DOI":"10.3390\/microorganisms10061103"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev-med-042711-140023","article-title":"Staphylococcal Infections: Mechanisms of Biofilm Maturation and Detachment as Critical Determinants of Pathogenicity","volume":"64","author":"Otto","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"ref_45","unstructured":"Gulati, M., and Nobile, C.J. (2017). Candida albicans Biofilms. Candida albicans: Cellular and Molecular Biology, Springer. [2nd ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113296","DOI":"10.1016\/j.comptc.2021.113296","article-title":"DFT, NBO, HOMO-LUMO, NCI, Stability, Fukui Function and Hole\u2013Electron Analyses of Tolcapone","volume":"1202","author":"Isravel","year":"2021","journal-title":"Comput. Theor. Chem."},{"key":"ref_47","first-page":"135","article-title":"Synthesis and Spectroscopic Characterization of Pyrrole-2,3-Diones and Their Following Reactions with 1,2-Aromatic Diamines","volume":"5","author":"Koca","year":"2012","journal-title":"Org. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.saa.2011.10.055","article-title":"Quantum-Chemical, Spectroscopic and X-Ray Diffraction Studies of (E)-2-[(2-Bromophenyl)iminomethyl]-4-Trifluoromethoxyphenol","volume":"87","author":"Tanak","year":"2012","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Young, D.C. (2001). Computational Chemistry: A Practical Guide for Applying Techniques to Real-World Problems, Wiley-Interscience.","DOI":"10.1002\/0471220655"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1016\/j.bmc.2018.04.054","article-title":"Design, Synthesis and Evaluation of Benzoheterocycle Analogues as Potent Antifungal Agents Targeting CYP51","volume":"26","author":"Zhao","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00214-007-0310-x","article-title":"The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements","volume":"120","author":"Zhao","year":"2008","journal-title":"Theor. Chem. Acc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/(SICI)1097-461X(2000)78:3<186::AID-QUA6>3.0.CO;2-H","article-title":"Studies on Density Functional Theory for the Electron-Transfer Reaction Mechanism between M\u2013C6H6 and M+\u2013C6H6 Complexes in the Gas Phase","volume":"78","author":"Zhou","year":"2000","journal-title":"Int. J. Quantum Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"126660","DOI":"10.1016\/j.molliq.2024.126660","article-title":"DFT and Molecular Docking Research on the Effects of Lichen Metabolites","volume":"417","author":"Sert","year":"2025","journal-title":"J. Mol. Liq."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.saa.2014.01.068","article-title":"Quantum Mechanical and Spectroscopic (FT-IR, FT-Raman, 1H NMR and UV) Investigations of 2-(Phenoxymethyl)benzimidazole","volume":"125","author":"Mary","year":"2014","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.compbiolchem.2019.01.013","article-title":"Synthesis, Computational Quantum Chemical Study, In Silico ADMET and Molecular Docking Analysis, In Vitro Biological Evaluation of a Novel Sulfur Heterocyclic Thiophene Derivative Containing 1,2,3-Triazole and Pyridine Moieties as a Potential Human Topoisomerase Inhibitor","volume":"79","author":"Murugavel","year":"2019","journal-title":"Comput. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/jrs.2145","article-title":"Density functional study on the structural conformations and intramolecular charge transfer from the vibrational spectra of the anticancer drug combretastatin-A2","volume":"40","author":"Padmaja","year":"2009","journal-title":"J. Raman Spectrosc."},{"key":"ref_57","unstructured":"Pavia, D.L., Lampman, G.M., Kriz, G.S., and Vyvyan, J.R. (2015). Introduction to Spectroscopy, Cengage Learning. [5th ed.]."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.molstruc.2010.10.035","article-title":"FT-IR and FT-Raman Spectra, Vibrational Assignments, NBO Analysis and DFT Calculations of 2-Amino-4-Chlorobenzonitrile","volume":"985","author":"Sudha","year":"2011","journal-title":"J. Mol. Struct."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.saa.2008.03.019","article-title":"Molecular Structure and Vibrational Spectra of 3-Chloro-4-Fluorobenzonitrile by Ab Initio HF and Density Functional Method","volume":"71","author":"Sundaraganesan","year":"2008","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"113920","DOI":"10.1016\/j.comptc.2022.113920","article-title":"Electronic and Structure Conformational Analysis (HOMO-LUMO, MEP, NBO, ELF, LOL, AIM) of Hydrogen Bond Binary Liquid Crystal Mixture: DFT\/TD-DFT Approach","volume":"1217","author":"Sundaram","year":"2022","journal-title":"Comput. Theor. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s40203-023-00139-3","article-title":"Molecular Docking\/Dynamics Simulations, MEP Analysis, Bioisosteric Replacement and ADME\/T Prediction for Identification of Dual Targets Inhibitors of Parkinson\u2019s Disease with Novel Scaffold","volume":"11","author":"Mettai","year":"2023","journal-title":"Silico Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF02834015","article-title":"Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking","volume":"9","author":"Nadendla","year":"2004","journal-title":"Resonance"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_66","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (Gaussian 09, 2009). Gaussian 09, Revision B.01."},{"key":"ref_67","unstructured":"Dennington, R., Keith, T., and Millam, J. (GaussView, 2009). GaussView, Version 5."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1021\/jp045733a","article-title":"New Scale Factors for Harmonic Vibrational Frequencies Using the B3LYP Density Functional Method with the Triple-\u03b6 Basis Set 6-311+G(d,p)","volume":"109","author":"Andersson","year":"2005","journal-title":"J. Phys. Chem. A"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1021\/ct700248k","article-title":"Performance of B3LYP Density Functional Methods for a Large Set of Organic Molecules","volume":"4","author":"Jorgensen","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_70","unstructured":"BIOVIA, and Dassault Syst\u00e8mes (Discovery Studio Visualizer, 2021). Discovery Studio Visualizer, v21.1.0.20298."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8704","DOI":"10.1021\/ja101646k","article-title":"Structural Basis of Multivalent Binding to Wheat Germ Agglutinin","volume":"132","author":"Schwefel","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1021\/acs.jmedchem.2c01905","article-title":"New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus","volume":"66","author":"Durcik","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"W726","DOI":"10.1093\/nar\/gkac297","article-title":"SuperPred 3.0: Drug Classification and Target Prediction\u2014A Machine Learning Approach","volume":"50","author":"Gallo","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1039\/C8MD00472B","article-title":"ADMET-Score\u2014A Comprehensive Scoring Function for Evaluation of Chemical Drug-Likeness","volume":"10","author":"Guan","year":"2019","journal-title":"MedChemComm"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.drudis.2019.10.014","article-title":"A Drug-Likeness Toolbox Facilitates ADMET Study in Drug Discovery","volume":"25","author":"Jia","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.ejmech.2017.11.086","article-title":"Peptides Having Antimicrobial Activity and Their Complexes with Transition Metal Ions","volume":"143","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.biotechadv.2018.05.004","article-title":"Silver Bullets: A New Lustre on an Old Antimicrobial Agent","volume":"36","author":"Sim","year":"2018","journal-title":"Biotechnol. Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s11274-021-03070-x","article-title":"Nanoparticles as Therapeutic Options for Treating Multidrug-Resistant Bacteria: Research Progress, Challenges, and Prospects","volume":"37","author":"Mba","year":"2021","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0162-0134(02)00464-6","article-title":"Metal Binding and Structure\u2013Activity Relationship of the Metalloantibiotic Peptide Bacitracin","volume":"91","author":"Ming","year":"2002","journal-title":"J. Inorg. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BFb0025287","article-title":"The Bleomycins: Antitumor Copper-Binding Antibiotics","volume":"40","author":"Umezawa","year":"1980","journal-title":"Struct. Bond."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:25:44Z","timestamp":1779423944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":84,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31101641"],"URL":"https:\/\/doi.org\/10.3390\/molecules31101641","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}