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Published on: November 10, 2013
Design, synthesis and biological evaluation of chromenopyrimidines as potential cytotoxic agents
Nehal M El-Bakhshawangy1, Hala B El-Nassan1, Asmaa E Kassab1
1Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
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.
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