Design, synthesis, and biological evaluation of 2, 4-dichlorophenoxyacetamide chalcone hybrids as potential c-Met kinase inhibitors

c-Met is involved in cellular processes that lead to the development and progression of cancer. A series of 2, 4-dichlorophenoxyacetamide-chalcones were synthesized and evaluated for their antiproliferative activities against MCF-7, HT-29, and A549 cancer cell lines. Several compounds showed moderate-to-good antiproliferative activity against MCF-7 and A549 cell lines. Many compounds were inactive against the HT-29 cell line. Some selected compounds were tested against c-Met kinase using the ADP Glo (TM) assay and were found to possess IC50 < 10 mu M indicating good activity. Compound 6f was identified as a promising compound and evaluated further for its antiproliferative and antimigratory properties on MCF-7 and A549 cell lines using colony formation and wound healing assays, respectively. Compound 6f had long-term antiproliferative effects and exerted antimigratory activity on both cell lines. Compound 6f had better potential at inhibiting growth and migration in MCF-7 cells. Molecular docking studies indicated that these compounds bind to Met1160 from the hinge region. Furthermore, molecular dynamics simulation studies for compound 6f confirmed this finding. Docking-based selectivity studies showed that these compounds were more selective for c-Met kinase. [GRAPHICS] .

Automated summary

c-Met is involved in cellular processes related to cancer development and progression. A series of compounds showed moderate-to-good antiproliferative activities against MCF-7 and A549 cells, with compound 6f exhibiting potential in inhibiting growth and migration of MCF-7 cells.