Rational design and synthesis of novel 2-(substituted-2H-chromen-3-yl)-5-aryl-1H-imidazole derivatives as an anti-angiogenesis and anti-cancer agent

摘要

Based on earlier proven pharmacophore analogues of cancer a novel 2-(substituted-2H-chromen-3-yl)-5-aryl-1H-imidazoles (13-16) were rationally designed and synthesized by the reaction of chromene-3-carboxylic acids (10a-d) with substituted acyl bromides in the presence of TEA followed by refluxing with NH4OAc in toluene. Compounds 13-16 were screened in vitro for the inhibition of KRAS/Wnt and their anti-angiogenesis properties. Compound 16f has been identified as a potent anti-angiogenesis molecule, which can be considered as a new lead structure. The molecular docking analysis displayed the higher binding affinity of 16f with KRAS, Wnt and VEGF.