4¦Â-[4¡ä-(1-(Aryl)ureido)benzamide]podophyllotoxins as DNA topoisomerase I and II¦Á inhibitors and apoptosis inducing agents
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- 作者：Ahmed Kamal ; Paidakula Suresh ; M. Janaki Ramaiah ; T. Srinivasa Reddy ; Ravi Kumar Kapavarapu ; Bolla Narasimha Rao ; Syed Imthiajali ; T. Lakshminarayan Reddy ; S.N.C.V.L. Pushpavalli ; Nagula Shankaraiah ; Manika Pal-Bhadra
- 关键词：Etoposide ; Podophyllotoxin ; Cell cycle ; Cytotoxicity ; Topoisomerase-II¦Á enzyme ; Topoisomerase-I enzyme
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2013
- 出版时间：1 September, 2013
- 年：2013
- 卷：21
- 期：17
- 页码：5198-5208
- 全文大小：1795 K
文摘
A series of 4¦Â-[4¡ä-(1-(aryl)ureido)benzamide]podophyllotoxin congeners (11a-l) were synthesized and evaluated for their cytotoxic activity against six human cancer cell lines. Some of the compounds like 11a, 11h, 11k and 11l showed significant anti-proliferative activity in Colo-205 cells and were superior to etoposide. The flow-cytometric analysis studies indicated that these compounds show strong G1 cell cycle arrest, as well exhibited improved inhibitory activities on DNA topoisomerase I and II¦Á enzymes. These compounds induce apoptosis by up regulating caspase-3 protein as observed by ELISA and Western blotting analysis. In addition, a brief structure-activity relationship studies within the series along with docking results of representative compounds 11a, 11h, 11k, 11l were presented.