1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides: Synthesis, molecular modeling, evaluation of their anti-inflammatory activity and ulcerogenicity


Abdel-Aziz M., Beshr E. A., Abdel-Rahman I. M., Ozadali K., Tan O., Aly O. M.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.77, pp.155-165, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 77
  • Publication Date: 2014
  • Doi Number: 10.1016/j.ejmech.2014.03.001
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.155-165
  • Keywords: 1,2,4-Triazole, Anti-inflammatory, Ulcerogenicity, Histopathological investigation, Cyclooxygenase activity, Docking study, ANTICANCER ACTIVITY, ACID-DERIVATIVES, COX-2 INHIBITORS, DRUGS, CYCLOOXYGENASE-2, 1,2,4-TRIAZOLES, ANTIFUNGAL, POTENT
  • Hacettepe University Affiliated: Yes

Abstract

A series of novel 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides were synthesized and confirmed with different spectroscopic techniques. The prepared compounds exhibited remarkable anti-inflammatory activity that represents 38%-100% of indomethacin activity and 44%-115% of celecoxib activity after 3 h. The anilides 5a-1 and hydrazide 6 exhibit low incidence of gastric ulceration compared to indomethacin which was confirmed with histopathological investigation. In vitro COX-1/COX-2 inhibition studies showed compounds 4b (COX-1 IC50 = 45.9 mu M; COX-2 IC50 = 68.2 mu M) and 6 (COX-1 IC50 = 39.8 mu M; COX-2 IC50 = 46.3 mu M) are the most potent COX inhibitors in the tested compounds. The binding mode for some of the tested compounds to the enzymes was predicted using docking studies. (c) 2014 Elsevier Masson SAS. All rights reserved.