Synthesis and tumor inhibitory activity of novel coumarin analogs targeting angiogenesis and apoptosis

• Coumarin analogs (5a–j) were synthesized starting from hydroxy benzophenones.
• Compounds (5a–j) were screened for angioprevention and tumor inhibition activity.
• The tumor inhibitory mechanism was due to the antiangiogenesis and apoptosis.
• Finally compound 5c was identified as potent molecule.
• Compound 5c could be developed as a potent anticancer drug in the near future.

A sequence of coumarin analogs 5a–j was obtained by multi step synthesis from hydroxy benzophenones (1a–j). The in vitro antiproliferative effect of the title compounds was tested against Ehrlich ascites carcinoma (EAC) and Daltons lymphoma ascites (DLA) cell lines. Among the series, compound 5c with bromo group in the benzophenone moiety was endowed with excellent antiproliferative potency with significant IC50 value. Further, in vivo antitumor effect of compound 5c against murine EAC and solid DL tumor model system was evident by the extended survivality. The tumor inhibitory mechanism of compound 5c was due to the antiangiogenesis and promotion of apoptosis. These results suggest possible applications of compound 5c which could be developed as a potent anticancer drug in the near future.

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