Design, synthesis, and antifungal activities in vitro of novel tetrahydroisoquinoline compounds based on the structure of lanosterol 14 alpha-demethylase (CYP51) of fungi

作者：Zhu Ju; Lu Jiaguo; Zhou Youjun^*; Li Yaowu; Cheng Jun; Zheng Canhui

来源：Bioorganic & Medicinal Chemistry Letters, 2006, 16(20): 5285-5289.

DOI：10.1016/j.bmcl.2006.08.001

• CYP51 inhibitor
• antifungal activity
• tetrahydroisoquinoline
• design
• lanosterol 14 alpha-demethylase (CYP51)

Novel tetrahydroisoquinoline compounds were designed by coupling structure-based de novo design based on the structure of lanosterol 14 alpha-demethylase (CYP51). The chemical synthesis and the antifungal activities in vitro of them were reported. The results exhibited that all of the lead compounds showed potent antifungal activities, in which compounds 6 and 7 had equal or stronger antifungal activities against five test fungi than that of fluconazole. The studies presented here provided the antifungal lead compounds. The affinity of the lead molecules for CYP51 was mainly attributed to their non-bonding interaction with the apoprotein, which was different from the azole antifungal agents.

• 出版日期2006-10-15
• 单位中国人民解放军第二军医大学