{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:54:43Z","timestamp":1790589283112,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy","award":["PCD 771\/77\/11.01.2023"],"award-info":[{"award-number":["PCD 771\/77\/11.01.2023"]}]},{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy","award":["PCD 647\/68\/11.01.2024"],"award-info":[{"award-number":["PCD 647\/68\/11.01.2024"]}]},{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy","award":["PCD 776\/64\/13.01.2025"],"award-info":[{"award-number":["PCD 776\/64\/13.01.2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: In this study, we aimed to investigate the antimicrobial and antibiofilm activity of seven hydroxyphenyl-thiazolyl-coumarin hybrid compounds with antioxidant properties (1a\u2013g), previously reported by our group. Methods: The compounds were evaluated in vitro through MIC, MBC, and MFC determinations, and percentage of biofilm (BF) inhibition and in silico, respectively, through molecular docking, molecular dynamics simulations, and ADMETox prediction. Results: All compounds showed antibacterial and antifungal activities. In terms of antibacterial activity, all the compounds were active on Pseudomonas aeruginosa (MICs = 15.62\u201331.25 \u03bcg\/mL), Enterococcus faecalis (MICs = 15.62\u201331.25 \u03bcg\/mL), and Staphylococcus aureus (MICs = 62.5\u2013125 \u03bcg\/mL). Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole (MIC = 15.62 \u03bcg\/mL), compounds 1b and 1g being the most active against Aspergillus brasiliensis (MIC = 15.62 \u03bcg\/mL). Furthermore, all compounds were both bactericidal and fungicidal. Regarding the antibiofilm activity, compounds 1d\u2013g showed superior P. aeruginosa BF inhibition compared to gentamicin. The in vitro results for the antibacterial activity were well correlated with the observations drawn in the molecular docking studies, where the best binding affinities (BAs) were observed against P. aeruginosa PAO1 GyrB subunit, and the molecular dynamics simulations confirmed the antibacterial mechanism of compounds 1a, 1b, 1d, 1f, and 1g through GyrB subunit inhibition. Regarding the antifungal activity, all compounds showed better BAs than fluconazole against CYP51 in all instances. ADMETox predictions concluded that all the compounds could have low gastrointestinal absorption and reduced risk of pharmacokinetic interactions. Conclusions: The investigated compounds bring novelty into the actual research due to their dual antibacterial and antibiofilm activity against biofilm-associated P. aeruginosa infections.<\/jats:p>","DOI":"10.3390\/antibiotics14090943","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:54:26Z","timestamp":1758200066000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antimicrobial and Antibiofilm Activities of Some Antioxidant 3,4-Dihydroxyphenyl-Thiazole-Coumarin Hybrid Compounds: In Silico and In Vitro Evaluation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5980-6963","authenticated-orcid":false,"given":"Daniel","family":"Ungureanu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0388","authenticated-orcid":false,"given":"Gabriel","family":"Marc","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-7425","authenticated-orcid":false,"given":"Mihaela Niculina","family":"Duma","sequence":"additional","affiliation":[{"name":"State Veterinary Laboratory for Animal Health and Safety, 1 Pia\u021ba M\u0103r\u0103\u0219ti Street, 400609 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-1460","authenticated-orcid":false,"given":"Radu","family":"Tamaian","sequence":"additional","affiliation":[{"name":"ICSI Business, National Institute for Research and Development for Cryogenic and Isotopic Technologies\u2014ICSI Rm. V\u00e2lcea, 4 Uzinei Street, 240050 R\u00e2mnicu V\u00e2lcea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-8071","authenticated-orcid":false,"given":"Dan Cristian","family":"Vodnar","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, 3\u20135 Calea M\u0103n\u0103\u0219tur, 400372 Cluj-Napoca, Romania"},{"name":"Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 3\u20135 Calea M\u0103n\u0103\u0219tur, 400372 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-5649","authenticated-orcid":false,"given":"Br\u00eendu\u0219a","family":"Tiperciuc","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Ionu\u021b","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8453-3642","authenticated-orcid":false,"given":"Anca","family":"Stana","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidiu","family":"Oniga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ungureanu, D., Oniga, O., Moldovan, C., Ionu\u021b, I., Marc, G., Stana, A., Pele, R., Duma, M., and Tiperciuc, B. (2024). An Insight into Rational Drug Design: The Development of In-House Azole Compounds with Antimicrobial Activity. Antibiotics, 13.","DOI":"10.3390\/antibiotics13080763"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ungureanu, D., Tiperciuc, B., Nastas\u0103, C., Ionu\u021b, I., Marc, G., Oniga, I., and Oniga, O. (2024). An Overview of the Structure\u2013Activity Relationship in Novel Antimicrobial Thiazoles Clubbed with Various Heterocycles (2017\u20132023). Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010089"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1128\/AAC.01203-10","article-title":"Nitric Oxide Protects Bacteria from Aminoglycosides by Blocking the Energy-Dependent Phases of Drug Uptake","volume":"55","author":"McCollister","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4155\/fmc.13.189","article-title":"Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms","volume":"6","author":"Delattin","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vaishampayan, A., and Grohmann, E. (2022). Antimicrobials Functioning through ROS-Mediated Mechanisms: Current Insights. Microorganisms, 10.","DOI":"10.3390\/microorganisms10010061"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1007\/s00210-023-02490-w","article-title":"A Review on Oxidant and Antioxidant Effects of Antibacterial Agents: Impacts on Bacterial Cell Death and Division and Therapeutic Effects or Adverse Reactions in Humans","volume":"396","author":"Delghandi","year":"2023","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14069","DOI":"10.1039\/D2RA01929A","article-title":"Potential Antimicrobial, Antidiabetic, Catalytic, Antioxidant and ROS\/RNS Inhibitory Activities of Silybum Marianum Mediated Biosynthesized Copper Oxide Nanoparticles","volume":"12","author":"Iqbal","year":"2022","journal-title":"RSC Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22188","DOI":"10.3390\/molecules201219841","article-title":"Study of the Relationships between the Structure, Lipophilicity and Biological Activity of Some Thiazolyl-Carbonyl-Thiosemicarbazides and Thiazolyl-Azoles","volume":"20","author":"Tamaian","year":"2015","journal-title":"Molecules"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lemilemu, F., Bitew, M., Demissie, T.B., Eswaramoorthy, R., and Endale, M. (2021). Synthesis, Antibacterial and Antioxidant Activities of Thiazole-Based Schiff Base Derivatives: A Combined Experimental and Computational Study. BMC Chem., 15.","DOI":"10.1186\/s13065-021-00791-w"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Al-Majedy, Y., Al-Duhaidahawi, D., Al-Azawi, K., Al-Amiery, A., Kadhum, A., and Mohamad, A. (2016). Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies. Molecules, 21.","DOI":"10.3390\/molecules21020135"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5530\/srp.2017.1.6","article-title":"Antioxidant Activity of Coumarins","volume":"8","author":"Kadhum","year":"2016","journal-title":"Syst. Rev. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Login, C.C., B\u00e2ldea, I., Tiperciuc, B., Benedec, D., Vodnar, D.C., Decea, N., and Suciu, \u015e. (2019). A Novel Thiazolyl Schiff Base: Antibacterial and Antifungal Effects and In Vitro Oxidative Stress Modulation on Human Endothelial Cells. Oxidative Med. Cell. Longev., 2019.","DOI":"10.1155\/2019\/1607903"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1601-1546.2012.00277.x","article-title":"Bacterial Biofilm: Structure, Function, and Antimicrobial Resistance","volume":"22","author":"Dufour","year":"2010","journal-title":"Endod. Top."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Todd, O.A., and Peters, B.M. (2019). Candida albicans and Staphylococcus aureus Pathogenicity and Polymicrobial Interactions: Lessons beyond Koch\u2019s Postulates. J. Fungi, 5.","DOI":"10.3390\/jof5030081"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Asma, S.T., Imre, K., Morar, A., Herman, V., Acaroz, U., Mukhtar, H., Arslan-Acaroz, D., Shah, S.R.A., and Gerlach, R. (2022). An Overview of Biofilm Formation\u2013Combating Strategies and Mechanisms of Action of Antibiofilm Agents. Life, 12.","DOI":"10.3390\/life12081110"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1021\/acsinfecdis.2c00469","article-title":"From Antibacterial to Antibiofilm Targeting: An Emerging Paradigm Shift in the Development of Quaternary Ammonium Compounds (QACs)","volume":"9","author":"Saverina","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1039\/D0NP00022A","article-title":"Natural Products as Inspiration for the Development of Bacterial Antibiofilm Agents","volume":"37","author":"Melander","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ejmech.2017.12.076","article-title":"Anti-Biofilm Effect of Novel Thiazole Acid Analogs against Pseudomonas aeruginosa through IQS Pathways","volume":"145","author":"Li","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s00044-013-0672-7","article-title":"Synthesis and Anti-Biofilm Activity of Thiazole Schiff Bases","volume":"23","author":"More","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1007\/s00253-018-8787-x","article-title":"Coumarin: A Novel Player in Microbial Quorum Sensing and Biofilm Formation Inhibition","volume":"102","author":"Reen","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Razaviamri, S., Wang, K., Liu, B., and Lee, B.P. (2021). Catechol-Based Antimicrobial Polymers. Molecules, 26.","DOI":"10.3390\/molecules26030559"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ungureanu, D., Marc, G., Tiperciuc, B., Moldovan, C., Ionu\u021b, I., Stana, A., Oniga, I., Vlase, L., P\u00eern\u0103u, A., and Oniga, O. (2025). Novel 3,4-Dihydroxyphenyl-Thiazole-Coumarin Hybrid Compounds: Synthesis, In Silico and In Vitro Evaluation of Their Antioxidant Activity. Antioxidants, 14.","DOI":"10.3390\/antiox14060636"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00706-021-02800-z","article-title":"GyrB Inhibitors as Potential Antibacterial Agents: A Review","volume":"152","author":"Gurram","year":"2021","journal-title":"Monatshefte Chem. Chem. Mon."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chauhan, S.S., Thaseen, E.A., and Parthasarathi, R. (2024). Computational Discovery of Potent Escherichia Coli DNA Gyrase Inhibitor: Selective and Safer Novobiocin Analogues. Comput. Toxicol., 29.","DOI":"10.1016\/j.comtox.2024.100302"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2478\/v10181-011-0123-7","article-title":"Susceptibility Testing of Aspergillus Niger Strains Isolated from Poultry to Antifungal Drugs\u2014A Comparative Study of the Disk Diffusion, Broth Microdilution (M 38-A) and Etest\u00ae Methods","volume":"15","author":"Tokarzewski","year":"2012","journal-title":"Pol. J. Vet. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1073\/pnas.73.12.4474","article-title":"Novobiocin and Coumermycin Inhibit DNA Supercoiling Catalyzed by DNA Gyrase","volume":"73","author":"Gellert","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nastas\u0103, C., Vodnar, D., Ionu\u0163, I., Stana, A., Benedec, D., Tamaian, R., Oniga, O., and Tiperciuc, B. (2018). Antibacterial Evaluation and Virtual Screening of New Thiazolyl-Triazole Schiff Bases as Potential DNA-Gyrase Inhibitors. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010222"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Stana, A., Vodnar, D.C., Tamaian, R., P\u00eern\u0103u, A., Vlase, L., Ionu\u021b, I., Oniga, O., and Tiperciuc, B. (2017). Design, Synthesis and Antifungal Activity Evaluation of New Thiazolin-4-Ones as Potential Lanosterol 14\u03b1-Demethylase Inhibitors. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010177"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.4155\/fmc-2017-0327","article-title":"Synthesis and Biological Evaluation of 2-Aminothiazole-Thiazolidinone Conjugates as Potential Antitubercular Agents","volume":"10","author":"Eldehna","year":"2018","journal-title":"Future Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nyerges, A., Toma\u0161i\u010d, T., Durcik, M., Revesz, T., Szili, P., Draskovits, G., Bogar, F., Skok, \u017d., Zidar, N., and Ila\u0161, J. (2020). Rational Design of Balanced Dual-Targeting Antibiotics with Limited Resistance. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000819"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1021\/acs.jmedchem.2c01597","article-title":"Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter Baumannii and Pseudomonas aeruginosa","volume":"66","author":"Cotman","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Keniya, M.V., Sabherwal, M., Wilson, R.K., Woods, M.A., Sagatova, A.A., Tyndall, J.D.A., and Monk, B.C. (2018). Crystal Structures of Full-Length Lanosterol 14\u03b1-Demethylases of Prominent Fungal Pathogens Candida Albicans and Candida Glabrata Provide Tools for Antifungal Discovery. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.01134-18"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6728","DOI":"10.1074\/jbc.M117.778308","article-title":"Structural Analyses of Candida Albicans Sterol 14\u03b1-Demethylase Complexed with Azole Drugs Address the Molecular Basis of Azole-Mediated Inhibition of Fungal Sterol Biosynthesis","volume":"292","author":"Hargrove","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1128\/AAC.00925-15","article-title":"Structural Insights into Binding of the Antifungal Drug Fluconazole to Saccharomyces Cerevisiae Lanosterol 14\u03b1-Demethylase","volume":"59","author":"Sagatova","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.bmcl.2012.11.032","article-title":"Pyrrolopyrimidine Inhibitors of DNA Gyrase B (GyrB) and Topoisomerase IV (ParE). Part I: Structure Guided Discovery and Optimization of Dual Targeting Agents with Potent, Broad-Spectrum Enzymatic Activity","volume":"23","author":"Tari","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","unstructured":"Nastas\u0103, C., Tamaian, R., Oniga, O., and Tiperciuc, B. (2019). 5-Arylidene(Chromenyl-Methylene)-Thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma. Medicina, 55.","DOI":"10.3390\/medicina55040085"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules","volume":"11","author":"Daina","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/minf.201400127","article-title":"In Silico Estimation of Chemical Carcinogenicity with Binary and Ternary Classification Methods","volume":"34","author":"Li","year":"2015","journal-title":"Mol. Inform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.1039\/C6RA25267B","article-title":"In Silico Prediction of Serious Eye Irritation or Corrosion Potential of Chemicals","volume":"7","author":"Wang","year":"2017","journal-title":"RSC Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.tiv.2019.01.004","article-title":"Prediction of the Skin Sensitising Potential and Potency of Compounds via Mechanism-Based Binary and Ternary Classification Models","volume":"59","author":"Di","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1021\/acs.chemrestox.5b00465","article-title":"Computational Models for Human and Animal Hepatotoxicity with a Global Application Scope","volume":"29","author":"Mulliner","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, Z., Zhao, P., Zhang, X., Xu, X., Li, W., Liu, G., and Tang, Y. (2021). In Silico Prediction of Chemical Respiratory Toxicity via Machine Learning. Comput. Toxicol., 18.","DOI":"10.1016\/j.comtox.2021.100155"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/jat.3772","article-title":"In Silico Prediction of Chemical Reproductive Toxicity Using Machine Learning","volume":"39","author":"Jiang","year":"2019","journal-title":"J. Appl. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/bioinformatics\/bty707","article-title":"AdmetSAR 2.0: Web-Service for Prediction and Optimization of Chemical ADMET Properties","volume":"35","author":"Yang","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/10629360802083871","article-title":"An Evaluation of the Implementation of the Cramer Classification Scheme in the Toxtree Software","volume":"19","author":"Patlewicz","year":"2008","journal-title":"SAR QSAR Environ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: The DrugBank Knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/jac\/dkw364","article-title":"Ciprofloxacin Selects for RNA Polymerase Mutations with Pleiotropic Antibiotic Resistance Effects","volume":"72","author":"Pietsch","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ejmech.2018.01.078","article-title":"Ciprofloxacin Derivatives and Their Antibacterial Activities","volume":"146","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_51","unstructured":"(2025, March 11). Determination That ALBAMYCIN (Novobiocin Sodium) Capsule, 250 Milligrams, Was Withdrawn from Sale for Reasons of Safety or Effectiveness, Available online: https:\/\/www.federalregister.gov\/documents\/2011\/01\/19\/2011-1000\/determination-that-albamycin-novobiocin-sodium-capsule-250-milligrams-was-withdrawn-from-sale-for."},{"key":"ref_52","unstructured":"(2025, March 11). 21 CFR 216.24\u2014Drug Products Withdrawn or Removed from the Market for Reasons of Safety or Effectiveness, Available online: https:\/\/www.ecfr.gov\/current\/title-21\/part-216\/section-216.24."},{"key":"ref_53","unstructured":"Constable, P.D., Hinchcliff, K.W., Done, S.H., and Gr\u00fcnberg, W. (2017). Practical Antimicrobial Therapeutics. Veterinary Medicine, Elsevier."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1365-2958.1993.tb01728.x","article-title":"The Interaction between Coumarin Drugs and DNA Gyrase","volume":"9","author":"Maxwell","year":"1993","journal-title":"Mol. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.1021\/bi952888n","article-title":"The Interaction of Coumarin Antibiotics with Fragments of the DNA Gyrase B Protein","volume":"35","author":"Gormley","year":"1996","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1128\/AAC.31.12.1925","article-title":"Effect of DNA Gyrase Inhibitors Pefloxacin, Five Other Quinolones, Novobiocin, and Clorobiocin on Escherichia coli Topoisomerase I","volume":"31","author":"Tabary","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D1465","DOI":"10.1093\/nar\/gkad751","article-title":"TTD: Therapeutic Target Database Describing Target Druggability Information","volume":"52","author":"Zhou","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kowalska-Krochmal, B., and Dudek-Wicher, R. (2021). The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. Pathogens, 10.","DOI":"10.3390\/pathogens10020165"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"de Castro, R.D., de Souza, T.M.P.A., Bezerra, L.M.D., Ferreira, G.L.S., de Brito Costa, E.M.M., and Cavalcanti, A.L. (2015). Antifungal Activity and Mode of Action of Thymol and Its Synergism with Nystatin against Candida Species Involved with Infections in the Oral Cavity: An in Vitro Study. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0947-2"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ejmech.2018.09.009","article-title":"Antibacterial and Antioxidant Activities for Natural and Synthetic Dual-Active Compounds","volume":"158","author":"Martelli","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chua, S.L., Ding, Y., Liu, Y., Cai, Z., Zhou, J., Swarup, S., Drautz-Moses, D.I., Schuster, S.C., Kjelleberg, S., and Givskov, M. (2016). Reactive Oxygen Species Drive Evolution of Pro-Biofilm Variants in Pathogens by Modulating Cyclic-Di-GMP Levels. Open Biol., 6.","DOI":"10.1098\/rsob.160162"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rajakumari, K., Aravind, K., Balamugundhan, M., Jagadeesan, M., Somasundaram, A., Brindha Devi, P., and Ramasamy, P. (2024). Comprehensive Review of DNA Gyrase as Enzymatic Target for Drug Discovery and Development. Eur. J. Med. Chem. Rep., 12.","DOI":"10.1016\/j.ejmcr.2024.100233"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.fct.2018.02.042","article-title":"The Antioxidant Activity of a Prenyl Flavonoid Alters Its Antifungal Toxicity on Candida Albicans Biofilms","volume":"114","author":"Peralta","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.phymed.2015.07.003","article-title":"Antifungal Activity of a Prenylated Flavonoid from Dalea Elegans against Candida Albicans Biofilms","volume":"22","author":"Peralta","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1016\/j.ijbiomac.2020.09.037","article-title":"The Assessment of Antibiofilm Activity of Chitosan-Zinc Oxide-Gentamicin Nanocomposite on Pseudomonas aeruginosa and Staphylococcus aureus","volume":"163","author":"Hemmati","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Morita, Y., Tomida, J., and Kawamura, Y. (2014). Responses of Pseudomonas aeruginosa to Antimicrobials. Front. Microbiol., 4.","DOI":"10.3389\/fmicb.2013.00422"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Torres, N.S., Montelongo-Jauregui, D., Abercrombie, J.J., Srinivasan, A., Lopez-Ribot, J.L., Ramasubramanian, A.K., and Leung, K.P. (2018). Antimicrobial and Antibiofilm Activity of Synergistic Combinations of a Commercially Available Small Compound Library with Colistin Against Pseudomonas aeruginosa. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02541"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bonincontro, G., Scuderi, S.A., Marino, A., and Simonetti, G. (2023). Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Pharmaceuticals\u00a02023, 16, 1531. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111531"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000081990","article-title":"Rifaximin, a Poorly Absorbed Antibiotic: Pharmacology and Clinical Potential","volume":"51","author":"Scarpignato","year":"2005","journal-title":"Chemotherapy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1046\/j.1365-2125.1998.00721.x","article-title":"Cytochrome P4502C9: An Enzyme of Major Importance in Human Drug Metabolism","volume":"45","author":"Miners","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_71","first-page":"966","article-title":"Ciprofloxacin","volume":"Volume 1","author":"Broderick","year":"2014","journal-title":"Encyclopedia of Toxicology"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Campbell, K.B. (2022). Antimicrobial Agents and Torsades de Pointes. Torsades de Pointes, Elsevier.","DOI":"10.1016\/B978-0-12-821446-6.00012-2"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jscs.2017.04.007","article-title":"Synthesis of 2-Phenylamino-Thiazole Derivatives as Antimicrobial Agents","volume":"21","author":"Bikobo","year":"2017","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mohammed, T.K., Aqel, N., and Al-Dujaili, E.A.S. (2020). Antimicrobial Activity of Liquid Residues of Cymbopogon Citratus Oil Extracts. J. Phys. Conf. Ser., 1660.","DOI":"10.1088\/1742-6596\/1660\/1\/012006"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"O\u2019Toole, G.A. (2011). Microtiter Dish Biofilm Formation Assay. J. Vis. Exp., 47.","DOI":"10.3791\/2437-v"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kadiri, F., Ezaouine, A., Blaghen, M., Bennis, F., and Chegdani, F. (2024). Antibiofilm Potential of Biosurfactant Produced by Bacillus Aerius against Pathogen Bacteria. Biocatal. Agric. Biotechnol., 56.","DOI":"10.1016\/j.bcab.2023.102995"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.sajb.2024.01.055","article-title":"In Vitro Antibiofilm and Quorum Sensing Inhibition Activities of Selected South African Plants with Efficacy against Bovine Mastitis Pathogens","volume":"166","author":"Akinboye","year":"2024","journal-title":"S. Afr. J. Bot."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"Bateman","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","article-title":"UniProt: The Universal Protein Knowledgebase in 2025","volume":"53","author":"Bateman","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_80","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_81","unstructured":"Berman, H.M. (2003). The Protein Data Bank. Leadership in Science and Technology: A Reference Handbook, SAGE Publications, Inc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.sbi.2015.08.001","article-title":"High-Resolution Protein\u2013Protein Docking by Global Optimization: Recent Advances and Future Challenges","volume":"35","author":"Park","year":"2015","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1021\/jm0300330","article-title":"Information Decay in Molecular Docking Screens against Holo, Apo, and Modeled Conformations of Enzymes","volume":"46","author":"McGovern","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1021\/ci9003943","article-title":"Recipes for the Selection of Experimental Protein Conformations for Virtual Screening","volume":"50","author":"Rueda","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Roy, K., Kar, S., and Das, R.N. (2015). Other Related Techniques. Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment, Elsevier.","DOI":"10.1016\/B978-0-12-801505-6.00010-7"},{"key":"ref_86","unstructured":"Stanzione, F., Giangreco, I., and Cole, J.C. (2021). Use of Molecular Docking Computational Tools in Drug Discovery. Progress in Medicinal Chemistry, Elsevier."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure Visualization for Researchers, Educators, and Developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Meng, E.C., Goddard, T.D., Pettersen, E.F., Couch, G.S., Pearson, Z.J., Morris, J.H., and Ferrin, T.E. (2023). UCSF ChimeraX: Tools for Structure Building and Analysis. Protein Sci., 32.","DOI":"10.1002\/pro.4792"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Dallakyan, S., and Olson, A.J. (2015). Small-Molecule Library Screening by Docking with PyRx. Methods in Molecular Biology, Human Press.","DOI":"10.1007\/978-1-4939-2269-7_19"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Holland, J.H. (1992). Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence, The MIT Press.","DOI":"10.7551\/mitpress\/1090.001.0001"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Nocedal, J., and Wright, S.J. (1999). Sequential Quadratic Programming. Numerical Optimization, Springer.","DOI":"10.1007\/b98874"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM General Force Field: A Force Field for Drug-like Molecules Compatible with the CHARMM All-atom Additive Biological Force Fields","volume":"31","author":"Vanommeslaeghe","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cplett.2013.08.097","article-title":"Molecular Dynamics Simulations Reveal Insight into Key Structural Elements of Aaptamines as Sortase Inhibitors with Free Energy Calculations","volume":"585","author":"Lv","year":"2013","journal-title":"Chem. Phys. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.3390\/ijms16036217","article-title":"Molecular Dynamics Simulations of Acylpeptide Hydrolase Bound to Chlorpyrifosmethyl Oxon and Dichlorvos","volume":"16","author":"Jin","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"254","DOI":"10.31925\/farmacia.2023.2.4","article-title":"Synthesis and In Silico Approaches of New Symmetric Bis-Thiazolidine-2,4-Diones as Ras and Raf Oncoproteins Inhibitors","volume":"71","author":"Marc","year":"2023","journal-title":"Farmacia"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Manolov, S., Bojilov, D., Ivanov, I., Marc, G., Bataklieva, N., Oniga, S., Oniga, O., and Nedialkov, P. (2023). Synthesis, Molecular Docking, Molecular Dynamics Studies, and In Vitro Biological Evaluation of New Biofunctional Ketoprofen Derivatives with Different N-Containing Heterocycles. Processes, 11.","DOI":"10.3390\/pr11061837"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1021\/ci300367a","article-title":"AdmetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET Properties","volume":"52","author":"Cheng","year":"2012","journal-title":"J. Chem. Inf. 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