551. Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I
- Author
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Wenya Wang, Wenfeng Liu, Jianzhong Yao, Hao Feng, Zhenyuan Miao, Chunquan Sheng, Xiaoying Che, Chuan Luo, Lingjian Zhu, Wannian Zhang, Yulan Xu, Jing Zhang, Wei Guo, and Pengfei Cheng
- Subjects
Stereochemistry ,Antineoplastic Agents ,Topoisomerase-I Inhibitor ,Chemical synthesis ,Benzylidene Compounds ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,medicine ,Structure–activity relationship ,Humans ,Enzyme Inhibitors ,Cytotoxicity ,Pharmacology ,biology ,Chemistry ,Topoisomerase ,Organic Chemistry ,Biological activity ,General Medicine ,DNA ,Biochemistry ,DNA Topoisomerases, Type I ,Enzyme inhibitor ,biology.protein ,Topotecan ,Camptothecin ,Topoisomerase I Inhibitors ,medicine.drug - Abstract
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 IC50 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. more...
- Published
- 2009