Aim: Imatinib possesses various mechanisms for combating cancer, making the development of imatinib analogs an attractive target for cancer research.
Method: Two series of analogs were designed and synthesized, maintaining the essential pharmacophoric features in imatinib structure. The synthesized compounds were subjected to cell-based antiproliferative assays against nonsmall lung (A549) and colon cancer cell lines. In addition, flow cytometry cell cycle and caspase-3 colorimetric assays were performed.
Results: Most compounds showed potent anticancer activity against both cell lines with IC50 = 0.14-5.07 μM. Three compounds demonstrated ability to reinforce cell cycle arrest at G1 stage in a manner similar to imatinib. In addition, they induced apoptosis via activation of caspase-3.
Keywords: 3D QSAR pharmacophore; caspase-3 induction; cytotoxicity; imatinib; protein kinase.