{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:01:20Z","timestamp":1782212480628,"version":"3.54.5"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["24H01322"],"award-info":[{"award-number":["24H01322"]}]},{"name":"JSPS KAKENHI","award":["JPMJFR205X"],"award-info":[{"award-number":["JPMJFR205X"]}]},{"name":"JST FOREST Program","award":["24H01322"],"award-info":[{"award-number":["24H01322"]}]},{"name":"JST FOREST Program","award":["JPMJFR205X"],"award-info":[{"award-number":["JPMJFR205X"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Nakaseomyces glabrata (Candida glabrata), the second most prevalent Candida pathogen globally, has emerged as a major clinical threat due to its ability to develop high-level azole resistance. In this study, two new 5,6-dihydrotetrazolo[1,5-c]quinazoline derivatives (c11 and c12) were synthesized and characterized using IR, LC-MS, 1H, and 13C NMR spectra. Along with 13 previously reported analogues, these compounds underwent in vitro antifungal testing against clinical N. glabrata isolates using a serial dilution method (0.125\u201364 mg\/L). Remarkably, compounds c5 and c1 exhibited potent antifungal activity, with minimum inhibitory concentrations of 0.37 \u03bcM and 0.47 \u03bcM, respectively\u2014about a 20-fold improvement in \u03bcM concentration over standard drugs like amphotericin B, caspofungin, and micafungin. A detailed structure\u2013activity relationship analysis revealed crucial molecular features enhancing antifungal potency. Extensive molecular docking studies across 18 protein targets explored potential binding pockets and affinities of the lead compounds. A robust 3D-QSAR model, incorporating molecular descriptors Mor26m and Mor29e, displayed good predictive ability for antifungal activity. In silico predictions indicated an absence of herbicidal effect, negligible environmental toxicity (to honeybees, avian species, and aquatic organisms), and mild human toxicity concerns for these compounds. This comprehensive approach aims to develop novel and effective antifungal compounds against the clinically relevant pathogen N. glabrata.<\/jats:p>","DOI":"10.3390\/jof10120816","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T11:25:33Z","timestamp":1732533933000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Fifteen 5,6-Dihydrotetrazolo[1,5-c]quinazolines Against Nakaseomyces glabrata: Integrating In Vitro Studies, Molecular Docking, QSAR, and In Silico Toxicity Assessments"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0057-1551","authenticated-orcid":false,"given":"Lyudmyla","family":"Antypenko","sequence":"first","affiliation":[{"name":"Independent Researcher, Lamana 11, 69063 Zaporizhzhia, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-445X","authenticated-orcid":false,"given":"Oleksii","family":"Antypenko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical, Organic, and Bioorganic Chemistry, Zaporizhzhia State Medical and Pharmaceutical University, M. Prymachenko Ave. 26, 69035 Zaporizhzhia, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Fominichenko","sequence":"additional","affiliation":[{"name":"Bacteriological Laboratory, Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council, Orikhivs\u2019ke Hwy. 10, 69600 Zaporizhzhia, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Karnaukh","sequence":"additional","affiliation":[{"name":"Bacteriological Laboratory, Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council, Orikhivs\u2019ke Hwy. 10, 69600 Zaporizhzhia, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8017-9108","authenticated-orcid":false,"given":"Serhii","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Research Institute of Chemistry and Geology, Oles Honchar Dnipro National University, Nauky Ave. 72, 49010 Dnipro, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieko","family":"Arisawa","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Biotechnologies, Graduate School of Bioresources and Bioenvironment Sciences, Kyushu University, 744 W5-674, Motooka Nishi-ku, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/infdis\/21.4.341","article-title":"Yeast-Like Fungi of the Human Intestinal Tract","volume":"21","author":"Anderson","year":"1917","journal-title":"J. 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