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Structure‐Activity Relationship, Cytotoxicity and Mode of Action of 2‐Ester‐substituted 1,5‐Benzothiazepines as Potent Antifungal Agents
Author(s) -
Kang Wang,
Du Xingqiong,
Wang Lanzhi,
Hu Lijuan,
Dong Yuhuan,
Bian Yanqing,
Li Yuan
Publication year - 2013
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201300316
Subject(s) - chemistry , moiety , cytotoxicity , mode of action , cryptococcus neoformans , stereochemistry , antifungal , structure–activity relationship , biological activity , combinatorial chemistry , biochemistry , microbiology and biotechnology , in vitro , biology
Abstract 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 BV 2 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.