{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:11:39Z","timestamp":1792725099312,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of Istanbul University","award":["FBA-2021-37260"],"award-info":[{"award-number":["FBA-2021-37260"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In the present study, we designed and synthesized thiolated VK3 analogs (VK3a\u2013g) along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial structure\u2013activity relationship study on these VK3 analogs. In particular, four thiolated VK3 analogs exhibited superior biological potency against some Gram-positive bacterial strains, including Staphylococcus aureus (ATCC\u00ae 29213) and Enterococcus faecalis (ATCC\u00ae 29212). Next, all thiolated VK3 analogs were evaluated for their potential of cell growth inhibition on the NCI-60 cancer cell lines panel. This screening underlined that the thiolated VK3 analogs have no visible cytotoxicity on different cancer cell lines. The selected two thiolated VK3 analogs (VK3a and VK3b), having minimal hemolytic activity, which also have the lowest MIC values on S. aureus and E. faecalis, were further evaluated for their inhibition capacities on biofilm formation after evaluating their potential in vitro antimicrobial activity against each of the 20 clinically obtained resistant strains of Staphylococcus aureus. VK3b showed excellent antimicrobial activity against clinically resistant S. aureus isolates. Furthermore, the tested molecules showed nearly two log10 reduction in the viable cell count at six hours according to the time kill curve studies. Although these molecules decreased biofilm attachment about 50%, when sub-MIC concentrations were used these molecules increased the percentage of biofilm formation. The molecular docking of VK3a and VK3b in S. aureus thymidylate kinase was conducted in order to predict their molecular interactions. VK3a and VK3b exhibited excellent lead-likeness properties and pharmacokinetic profiles that qualify them for further optimization and development. In conclusion, since investigating efficient novel antimicrobial molecules is quite difficult, these studies are of high importance, especially in the present era of antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/ph15050586","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:30:28Z","timestamp":1652142628000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-6120","authenticated-orcid":false,"given":"Hatice","family":"Y\u0131ld\u0131r\u0131m","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul 34320, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Gebze Technical University, Gebze, Kocaeli 41400, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil\u00fcfer","family":"Bayrak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul 34320, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4428-5066","authenticated-orcid":false,"given":"Emel","family":"Matarac\u0131-Kara","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-2659","authenticated-orcid":false,"given":"Mohamed Osman","family":"Radwan","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"},{"name":"Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Tarbin","family":"Jannuzzi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"},{"name":"Department of Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-4052","authenticated-orcid":false,"given":"Mikako","family":"Fujita","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-1109","authenticated-orcid":false,"given":"Ama\u00e7 Fatih","family":"TuYuN","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Istanbul University, Fatih, Istanbul 34126, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1001\/jama.287.23.3116","article-title":"Vitamins for chronic disease prevention in adults: Scientific review","volume":"287","author":"Fairfield","year":"2002","journal-title":"JAMA"},{"key":"ref_2","first-page":"S29","article-title":"Potential Roles of Vitamins in the Management of COVID-19: A Comprehensive Review","volume":"27","author":"Rezaei","year":"2021","journal-title":"Pharm. 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