887139-22-2Relevant academic research and scientific papers
Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and molecular docking
Sheng, Chunquan,Zhang, Wannian,Ji, Haitao,Zhang, Min,Song, Yunlong,Xu, Hui,Zhu, Jie,Miao, Zhenyuan,Jiang, Qingfen,Yao, Jianzhong,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo
, p. 2512 - 2525 (2007/10/03)
In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods, CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14α-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals, π-π stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.
