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. U. , Aly O. M.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.77, ss.155-165, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 77
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.ejmech.2014.03.001
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.155-165

Özet

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.

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.