Design, Synthesis and Biological Evaluation of Chromenopyrimidines as Potential Cytotoxic Agents
- 21 May 2018
- journal article
- research article
- Published by Taylor & Francis in Future Medicinal Chemistry
- Vol. 10 (12) , 1465-1481
Abstract
Aim: The design and synthesis of chromenopyrimidines as microtubule destabilizing agents. Materials & methods: Novel chromenopyrimidines and chromenotriazolopyrimidines were prepared and evaluated for their cytotoxicity against MCF-7 cell line. The most potent compound was tested for its possible effect on tubulin inhibition, cell cycle distribution, apoptosis initiation and caspase-3 activation. Results: All the prepared compounds showed potent cytotoxic activity. Compound 13 was the most prominent (IC50 = 0.13 μM on tumor cell line MCF-7 and 14.06 μM on mammary epithelial cell line MCF-10A). Compound 13 inhibited tubulin polymerization (IC50 = 8.39 μM), caused cell cycle arrest at G2/M phase (fivefold more than control) and cellular apoptosis. Compound 13 increased the level of active caspase-3, 12-fold compared with control. Graphical abstractKeywords
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