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Acta Chimica Sinica ›› 2010, Vol. 68 ›› Issue (22): 2338-2346. Previous Articles Next Articles
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唐辉1,2,郑灿辉1,†,吕加国*,1,付丙月1,周有骏*,1,朱驹1
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国家自然科学基金项目;863计划
Tang Hui1,2 Zheng Canhui1,† Lü Jiaguo*,1 Fu Bingyue1 Zhou Youjun*,1 Zhu Ju1
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A series of novel pyrazino [2,1-a] isoquinolin compounds were designed and synthesized, and their antifungal activities in vitro were evaluated. All these compounds had potent antifungal activity against five pathogenic fungi. Compounds 5h, 5j~5l, 6g~6k, and 6l showed comparable or stronger inhibitory activities against nearly all the test fungi except Candida albicans than that of fluconazole. In particular, the most compounds exhibited activities with broad antifungal spectrum, and showed potent activities against Aspergillus fumigatus, which is not inhibited effectively by fluconazole. Moreover, the mode of action of the pyrazino [2,1-a] isoquinolin molecules showed that the affinity of the lead molecules for CYP51 was mainly attributed to their nonbonding interaction with the residues of apoprotein but without binding with the heme. These pyrazino [2,1-a] isoquinolin provided lead compounds for the development of antifungal drugs. The studies presented here provide a new structural type for the development of novel antifungal agents.
Key words: antifungal, lanosterol 14α-demethylase inhibitor, pyrazino [2,1-a] isoquinolin
TANG Hui, ZHENG Can-Hui, LV Jia-Guo, FU Bing-Yue, ZHOU You-Jun, ZHU Ju. Synthesis and Antifungal Activities in vitro of Novel Pyrazino [2,1-a] Isoquinolin Derivatives[J]. Acta Chimica Sinica, 2010, 68(22): 2338-2346.
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