Anti-inflammatory effect and inhibition of nitric oxide production by targeting COXs and iNOS enzymes with the 1,2-diphenylbenzimidazole pharmacophore

Mónica I. García-Aranda, Jazmin E. Gonzalez-Padilla, Carlos Z. Gómez-Castro, Yolanda M. Gómez-Gómez, Martha C. Rosales-Hernández, Efrén V. García-Báez, Marina O. Franco-Hernández, José L. Castrejón-Flores, Itzia I. Padilla-Martínez

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    Abstract

    Being the base of several non-communicable diseases, including cancer, inflammation is a complex process generated by tissue damage or change in the body homeostatic state. Currently, the therapeutic treatment for chronic inflammation related diseases is based on the use of selective cyclooxygenase II enzyme, COX-2, inhibitors or Coxibs, which have recently regained attention giving their preventive role in colon cancer. Thus, the discovery of new molecules that selectively inhibit COX-2 and other inflammatory mediators is a current challenge in the medicinal chemistry field. 1-Phenylbenzimidazoles have shown potential COX inhibitory activity, because they can reproduce the interaction profile of known COX inhibitors. Therefore, in the present investigation a series of 1,2-diphenylbenzimidazoles (DPBI) with different aromatic substitutions in the para position were synthesized and their interaction with COX-2 and nitric oxide synthase, iNOS, was determined in silico, in vitro and in vivo. Compound 2-(4-bromophenyl)-1-(4-nitrophenyl)-1H-benzo[d]imidazole showed the best inhibition towards COX-2, while compounds N-(4-(2-(4-bromophenyl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide and N-(4-(2-(4-chlorophenyl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide diminished the production of NO in vitro. Additionally, they had a significant anti-inflammatory activity in vivo when given orally.

    Original languageEnglish
    Article number115427
    JournalBioorganic and Medicinal Chemistry
    Volume28
    Issue number9
    DOIs
    StatePublished - 1 May 2020

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    Keywords

    • Anti-inflammatory
    • Benzimidazole
    • COX-inhibition
    • iNOS inhibition
    • Interaction profile of COX-2

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