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Design and Synthesis of Benzimidazole Analogs Endowed with Oxadiazole as Selective COX‐2 Inhibitor
Author(s) -
Rathore Ankita,
Rahman Mujeeb Ur,
Siddiqui Anees Ahamad,
Ali Abuzer,
Shaharyar Mohammad
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400219
Subject(s) - chemistry , benzimidazole , cyclooxygenase , in vivo , stereochemistry , aryl , in vitro , enzyme , docking (animal) , oxadiazole , cell culture , carrageenan , cytotoxicity , pharmacology , potency , lead compound , biochemistry , alkyl , medicine , organic chemistry , biology , genetics , microbiology and biotechnology , nursing
New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2‐(2‐((pyrimidin‐2‐ylthio)methyl)‐1 H ‐benzo[ d ]imidazol‐1‐yl)acetohydrazide as 1‐((5‐substituted alkyl/aryl‐1,3,4‐oxadiazol‐2‐yl)methyl)‐2‐((pyrimidin‐2‐ylthio)methyl)‐1 H ‐benzimidazoles ( 5a – r ) with the aim to acquire selective cyclooxygenase (COX‐2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX‐1 and COX‐2 inhibitory potency and the results showed that they had good‐to‐remarkable activity with an IC 50 range of 11.6–56.1 µM. The most active compounds were further screened for their in vivo anti‐inflammatory activity by using the carrageenan‐induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX‐2 inhibition with an IC 50 value of 8.2 µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO‐31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX‐2 inhibitors.