title: 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.
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-l 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 μM; COX-2 IC50 = 68.2 μM) and 6 (COX-1 IC50 = 39.8 μM; COX-2 IC50 = 46.3 μM) 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.
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Eman A
authors.initials: EA
authors.lastname: Beshr
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Islam M
authors.initials: IM
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
authors.forename: Keriman
authors.initials: K
authors.lastname: Ozadali
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
authors.forename: Oya Unsal
authors.initials: OU
authors.lastname: Tan
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Electronic address: omarsokkar@yahoo.com.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Aly
mesh_terms: D000818:Animals; D000840:Anisoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000138:chemical synthesis / Q000494:pharmacology*; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000593387:1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-(1,2,4)triazole-3-carboxylic acid hydrazide; C000593386:1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-(1,2,4)triazole-3-carboxylic acid methylamide; D000840:Anisoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006834:Hydrazines; D014230:Triazoles; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: 1,2,4-Triazole; Anti-inflammatory; Cyclooxygenase activity; Docking study; Histopathological investigation; Ulcerogenicity