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Topoisomerase I‐Mediated Antiproliferative Activity of 10‐Substituted and 12‐Substituted Homocamptothecins
Author(s) -
Guo Wei,
Liu Wenfeng,
Zhu Lingjian,
Zhang Yongqiang,
Cheng Pengfei,
Dong Guoqiang,
Zhuang Chunlin,
Yao Jianzhong,
Sheng Chunquan,
Miao Zhenyuan,
Zhang Wannian
Publication year - 2011
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.201000307
Subject(s) - camptothecin , topotecan , chemistry , topoisomerase , in vitro , cell culture , cytotoxic t cell , sn 38 , stereochemistry , positive control , pharmacology , irinotecan , biochemistry , cancer , traditional medicine , biology , chemotherapy , medicine , genetics , colorectal cancer
Homocamptothecin (hCPT) is an E ‐ring modified camptothecin (CPT) analogue, which showed pronounced inhibitory activity of topoisomerase I. In search of novel hCPT‐type anticancer agents, two series of hCPT derivatives were synthesized and evaluated in vitro against three human tumor cell lines. The results indicated that the 10‐substituted hCPT derivatives had a considerably higher cytotoxic activity than the 12‐substituted ones. Among the 10‐substituted compounds, 8a, 8b, 9b , and 9i showed an equivalent or even more potent activity than the positive control drug topotecan against the lung cancer cell line A‐549. Moreover, the hCPT analogues 8a and 8b exhibited a higher topoisomerase I inhibitory activity than CPT at a concentration of 100 μ M .