Synthesis and Antifungal Activities of Novel 2-Aminotetralin Derivatives

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• 作者：Bin Yao ; Haitao Ji ; Yongbin Cao ; Youjun Zhou ; Jü ; Zhu ; Jiaguo Lü ; Yaowu Li ; Jun Chen ; Canhui Zheng ; Yuanying Jiang ; Rongmei Liang ; Hui Tang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 1, 2007
• 年：2007
• 卷：50
• 期：22
• 页码：5293 - 5300
• 全文大小：245K
• 年卷期：v.50,no.22(November 1, 2007)
• ISSN：1520-4804

文摘

Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold waschemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Theirantifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs).Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing humanfungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine,ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol14-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide anew structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluatedin vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number offungal colony counts.