Design, Synthesis and Evaluation of Novel Benzimidazoles, Benzothiazoles and Benzofurans Incorporating Pyrazole Moiety as Antiangiogenic Agents

Abstract

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

Key words

Benzimidazole - benzothiazole - benzofuran and pyrazole derivatives - human umbilical vein endothelial cell (HUVEC) - vascular endothelial growth factor receptor (VEGF-2) - Antiangiogenic activity - Antiproliferative effect

• References

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