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Triazole derivatives with improved in vitro antifungal activity over azole drugs

Authors Yu S, Chai X, Wang Y, Cao Y, Zhang J, Wu Q, Zhang D, Jiang Y, Yan T, Sun Q

Received 3 December 2013

Accepted for publication 24 January 2014

Published 10 April 2014 Volume 2014:8 Pages 383—390

DOI https://doi.org/10.2147/DDDT.S58680

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2


Shichong Yu,1,* Xiaoyun Chai,1,* Yanwei Wang,1 Yongbing Cao,2 Jun Zhang,3 Qiuye Wu,1 Dazhi Zhang,1 Yuanying Jiang,2 Tianhua Yan,4 Qingyan Sun1

1Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 3Overseas Education Faculty of the Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China

*These authors contributed equally to this work

Abstract: A series of triazole antifungal agents with piperidine side chains was designed and synthesized. The results of antifungal tests against eight human pathogenic fungi in vitro showed that all the compounds exhibited moderate-to-excellent activities. Molecular docking between 8d and the active site of Candida albicans CYP51 was provided based on the computational docking results. The triazole interacts with the iron of the heme group. The difluorophenyl group is located in the S3 subsite and its fluorine atom (2-F) can form H-bonds with Gly307. The side chain is oriented into the S4 subsite and formed hydrophobic and van der Waals interactions with the amino residues. Moreover, the phenyl group in the side chain interacts with the phenol group of Phe380 through the formation of π–π face-to-edge interactions.

Keywords: synthesis, CYP51, molecular docking, azole agents

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