A series of novel ethyl 1-(2-(4-(2-amino-5-(ethoxycarbonyl) phenyl) piperazin-1-yl) ethyl)-2-(2-(substituted)
pyridin-3-yl)-1H-benzo[d]imidazole-5-carboxylate analogues were synthesized and screened as p38 MAP kinase inhibitors.
The 4-chlorophenoxy substitution in the 2nd position of the pyridyl moiety (5i) gave effective inhibition of p38 with
IC50 17µM. Moreover, the synthesized benzimidazole derivatives possess a significant antiproliferative activity against
blood-leukemia (CCRF-CEM), colon (HCT-116) and breast (MDA-MB-468) cancer cell lines. Based on the report, we
discussed structure-activity relationship (SAR) study of synthesized benzimidazole derivatives. Molecular modelling performed
for the identification of most active compounds by using three dimensional crystal structures of MAPK p38, provide
a disclosed binding template of these inhibitors in the active site of their respective enzyme.
Keywords: Benzimidazole, pyridine, MAPK p38, leukemia, colon cancer, breast cancer.
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