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

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

  • Bioorg Med Chem. 2020 May 1;28(9):115427. doi: 10.1016/j.bmc.2020.115427.
Mónica I García-Aranda 1,  Jazmin E Gonzalez-Padilla 2,  Carlos Z Gómez-Castro 3,  Yolanda M Gómez-Gómez 1,  Martha C Rosales-Hernández 2,  Efrén V García-Báez 1,  Marina O Franco-Hernández 1,  José L Castrejón-Flores 4,  Itzia I Padilla-Martínez 5
Affiliations

Affiliations

  • 1 Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología del Instituto Politécnico Nacional, Av. Acueducto s/n Barrio la Laguna Ticomán, Ciudad de México 07340, Mexico City, Mexico.
  • 2 Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, 11340 Mexico City, Mexico.
  • 3 CONACyT - Universidad Autónoma del Estado de Hidalgo, km 4.5 Carretera Pachuca-Tulancingo, Col. Carboneras, Mineral de la Reforma, Hidalgo 42184, Mexico.
  • 4 Laboratorio de Cultivo Celular y Biología Molecular, Unidad Profesional Interdisciplinaria de Biotecnología del Instituto Politécnico Nacional, Av. Acueducto s/n Barrio la Laguna Ticomán, Ciudad de México 07340, Mexico City, Mexico. Electronic address: jlcastrejon@ipn.mx.
  • 5 Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología del Instituto Politécnico Nacional, Av. Acueducto s/n Barrio la Laguna Ticomán, Ciudad de México 07340, Mexico City, Mexico. Electronic address: ipadillamar@ipn.mx.
PMID: 32205045 DOI: 10.1016/j.bmc.2020.115427
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.

Keywords

Anti-inflammatory; Benzimidazole; COX-inhibition; Interaction profile of COX-2; iNOS inhibition.

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