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2,4-Disubstituted Quinazoline Derivatives Act as Inducers of Tubulin Polymerization: Synthesis and Cytotoxicity.
Anti-cancer Agents in Medicinal Chemistry 2019 March 15
Considering the importance to find highly active anticancer agents, we investigated the synthesis and cytotoxic activity of twenty seven 2,4-disubstituted quinazoline derivatives. The cytotoxicity of compounds 1-27 was tested in SRB assays employing five different human tumor cell lines showing four compounds, 2, 9, 16 and 26, being highly cytotoxic with IC50 values ranging between 2.1 and 14.3 µM. The possible mode of action of compounds, 2, 9, 16 and 26, and the taxol binding site of the protein tubulin, an important goal for antimitotic drugs, was also studied by molecular docking followed by an investigation of the effects of compounds 9 and 16 on the polymerization of tubulin using a commercially available assay kit. The results showed the tested compounds to be highly active as inducers of tubulin polymerization.
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