Yu Shichong, Chai Xiaoyun, Wang Yanwei, Cao Yongbing, Zhang Jun, Wu Qiuye, Zhang Dazhi, Jiang Yuanying, Yan Tianhua, Sun Qingyan
Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2014 Apr 10;8:383-90. doi: 10.2147/DDDT.S58680. eCollection 2014.
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.
设计并合成了一系列带有哌啶侧链的三唑类抗真菌剂。体外对八种人类致病真菌的抗真菌测试结果表明，所有化合物均表现出中等至优异的活性。基于计算对接结果，给出了8d与白色念珠菌CYP51活性位点之间的分子对接情况。三唑与血红素基团的铁相互作用。二氟苯基位于S3亚位点，其氟原子（2-F）可与Gly307形成氢键。侧链朝向S4亚位点，并与氨基残基形成疏水和范德华相互作用。此外，侧链中的苯基通过形成π-π面对面相互作用与Phe380的酚基相互作用。
