Synthesis and evaluation of novel azoles as potent antifungal agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 1; pp. 192 - 194
• Main Authors: Li, Liangjing, Ding, Hao, Wang, Baogang, Yu, Shichong, Zou, Yan, Chai, Xiaoyun, Wu, Qiuye
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 01.01.2014
• Subjects: Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Aspergillus fumigatus; Azoles - chemical synthesis; Azoles - chemistry; Azoles - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Fungi - drug effects; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Antifungal activity; CASPOFUNGIN; Azole; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.11.037

Using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. The results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039 mu g/mL, followed by voriconazole, which has a MIC of 0.0625 mu g/mL. The 1,3,4-oxadiazole side chain is not the major contributor but plays a role in eliciting the observed antifungal activity. (C) 2013 Elsevier Ltd. All rights reserved.