Discovery of highly potent novel antifungal azoles by structure-based rational design
On the basis of the active site of lanosterol 14αdemethylase from Candida albicans (CACYP51), a series of new azoles were designed and synthesized. All the new azoles show excellent in vitro activity against most of the tested pathogenic fungi, which represent a class of promising leads for the development of novel antifungal agents. The MIC80 value of compounds 8c, 8i and 8n against C. albicans is 0.001 μg/mL indicating that these compounds are more potent than fluconazole, itraconazole and voriconazole. Flexible molecular docking was used to analyze the structure-activity relationships (SARs) of the compounds. The designed compounds interact with CACYP51 through hydrophobic, van der Waals and hydrogen-bonding interactions.
Wenya Wang Chunquan Sheng Xiaoying Che Haitao Ji Yongbing Cao Zhenyuan Miao Jianzhong Yao Wannian Zhang
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, Peoples Re Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA Department of Biochem
国际会议
武汉
英文
1-5
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）