Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I

A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives posse...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2010-06, Vol.45 (6), p.2223-2228
Main Authors: Guo, Wei, Miao, Zhenyuan, Sheng, Chunquan, Yao, Jianzhong, Feng, Hao, Zhang, Wannian, Zhu, Lingjian, Liu, Wenfeng, Cheng, Pengfei, Zhang, Jing, Che, Xiaoying, Wang, Wenya, Luo, Chuan, Xu, Yulan
Format: Article
Language:English
Subjects:
9-Benzylideneamino
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antitumor activity
Benzylidene Compounds - chemistry
Biological and medical sciences
Camptothecin - analogs & derivatives
Camptothecin - chemical synthesis
Camptothecin - chemistry
Camptothecin - pharmacology
Cell Line, Tumor
DNA - metabolism
DNA Topoisomerases, Type I - metabolism
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
General aspects
Homocamptothecin
Humans
Inhibitory Concentration 50
Medical sciences
Pharmacology. Drug treatments
Structure-Activity Relationship
Synthesis
Topoisomerase I Inhibitors
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Summary:A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds ( 6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC 50 values of 2.3 nM–9.8 nM against breast cancer cell than topotecan. As compared to CPT, compound 6f revealed higher topoisomerase I inhibitory activity. [Display omitted] A serial of novel 7-methyl-9-benzylideneamino derivatives of homocamptothecin are synthesized. Compounds 6c– o showed potent cytotoxic activity against A549, MDA-MB-435 and LOVO cell lines.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2010.01.063