Quinazoline is a privileged structure due to its presence in multiple approved drugs and its related biological activities. Analogues of this structure have been associated as potential leads for certain targets inhibitors such as: dihydrofolate reductase and tyrosine kinase receptors, among others. For the latter mentioned, quinazoline is an interesting scaffold structure for the treatment of certain types of cancer. Our research group had previously synthetized quinazoline-2,4,6-triamine derivatives with acceptable cytotoxic activity against different cancer cell lines. Based on these studies, we performed molecular docking studies of our in-house compounds in the nocodazole binding site of the β-tubulin and designed 12 novel quinazoline derivatives as potential tubulin polymerization inhibitors. In this work, we synthetized a set of 10 quinazoline derivatives varying the C6 position with poly-substituted quinolinyl, naphthyl and meta or disubstituted-phenyl groups. Our set of compounds were obtained by conventional and microwave aided methods, comparing their differences in terms of reaction yield, time, and chemical reactions involved. Currently, evaluation of these compounds is being determined in 5 different types of cancer cell lines such as: PC-3, HCT-15, MCF-7, MDAMB231 and SKLU. Appraising cellular viability, as a result of this biological assay, several compounds were identified to be very potent against these tumor cellular lines. Therefore, further biological assays will be carried out to determine the half maximal inhibitory concentrations (IC50) for the most potent compounds in only a few cell lines. To determine their possible mechanism as potential tubulin depolymerization activity, different experimental assays will be accomplished.

Quinazoline derivatives as potential tubulin polimerization inhibitors

2019 Spring National Meeting

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