Structure-Activity Relationship, Cytotoxicity and Mode of Action of 2-Ester-substituted 1,5-Benzothiazepines as Potent Antifungal Agents  

作　　者：Wang Kang Xingqiong Du Lanzhi Wang Lijuan HU Yuhuan Dong Yanqing Bian Yuan Li 

机构地区：[1]College of Chemistry & Material Science, Hebei Normal University, Sho'iazhuang, Hebei 050024, China [2]College of Life Sciences, Hebei Normal University, Sho'iazhuang, Hebei 050024, China [3]Department of Chemistry, Tangshan Normal University, Tangshan, Hebei 063000, China

出　　处：《Chinese Journal of Chemistry》2013年第10期1305-1314,共10页中国化学（英文版）

基　　金：Acknowledgement The authors gratefully acknowledge the financial support of the National Natural Science Foundation of China （No. 20972040）.

摘　　要：Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5- benzothiazepine （7a）. Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues （7a, 7b） were further studied by evaluating their cytotoxicity and mode of action （for 7a）. The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells.Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5- benzothiazepine （7a）. Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues （7a, 7b） were further studied by evaluating their cytotoxicity and mode of action （for 7a）. The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells.

关 键 词：1 5-benzothiazepines antifungal agents antifungal mechanism CYTOTOXICITY structure-activity relationships 

分 类 号：TQ457.29[化学工程—农药化工] Q959.133[生物学—动物学]