Design, synthesis and biological evaluation of chromenopyrimidines as potential cytotoxic agents

摘要

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=0.13M on tumor cell line MCF-7 and 14.06M on mammary epithelial cell line MCF-10A). Compound 13 inhibited tubulin polymerization (IC50=8.39M), 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.