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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Synthesis and Evaluation of Compounds Containing 4-arylpiperazinyl Moieties Linked to a 2-(pyridin-3-yl)-1H-benzimidazole as p38 MAP Kinase Inhibitors

Author(s): Mohamed Ashraf Ali, Hasnah Osman, Raju Suresh Kumar, Abdulrahman I. Almansour, Natarajan Arumugam, Vijay H. Masand and Theivendren Panneerselvam

Volume 13 , Issue 7 , 2016

Page: [691 - 696] Pages: 6

DOI: 10.2174/1570180812666151022221401

Price: $65


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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