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Synthesis and Biological Evaluation of 7‐Alkenyl Homocamptothecins as Potent Topoisomerase I Inhibitors
Author(s) -
Zhu Lingjian,
Zhang Xianghua,
Lei Ning,
Liu Wenfeng,
Miao Zhenyuan,
Zhuang Chunlin,
Sheng Chunquan,
Guo Wei,
Dong Guoqiang,
Yao Jianzhong,
Cheng Pengfei,
Zhang Wannian
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201100195
Subject(s) - camptothecin , topotecan , topoisomerase , chemistry , stereochemistry , lactone , in vitro , ring (chemistry) , cytotoxic t cell , cytotoxicity , cell culture , derivative (finance) , combinatorial chemistry , biochemistry , organic chemistry , chemotherapy , biology , genetics , economics , financial economics
Abstract Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven‐membered β ‐hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7‐alkenyl‐homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A‐549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I‐inhibition activity.