title: Novel 1-[4-(Aminosulfonyl)phenyl]-1H-1,2,4-triazole derivatives with remarkable selective COX-2 inhibition: design, synthesis, molecular docking, anti-inflammatory and ulcerogenicity studies.
abstract: A novel series of 1,2,4-triazole derivatives were synthesized and confirmed with different spectroscopic techniques. The prepared compounds exhibited remarkable anti-inflammatory activity comparable to that of indomethacin and celecoxib after 3 h. The tested compounds exhibited very low incidence of gastric ulceration compared to indomethacin. Most of the newly developed compounds showed excellent selectivity towards human COX-2 with selectivity indices (COX-1 IC50/COX-2 IC50) ranged from 62.5 to 2127. Docking studies results revealed that the highly selective tested compounds 6h and 6j showed lower CDOCKER energies, which means that they require less energy for proper interaction with the enzyme. The additional H-bonds with the oxygen of the amide and/or H of NH of the amide with the amino acid residues may be responsible for the higher binding affinity of this group of compounds towards COX-2.
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Gamal El-Din A A
authors.initials: Gel-D
authors.lastname: Abuo-Rahma
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Electronic address: abulnil@hotmail.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Abbassia, 11566 Cairo, Egypt.
authors.forename: Nahla A
authors.initials: NA
authors.lastname: Farag
authors.affiliation: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Tamer S
authors.initials: TS
authors.lastname: Kaoud
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced*; D013379:Substrate Specificity; D014230:Triazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000596336:1-(4-(aminosulfonyl)phenyl)-1H-1,2,4-triazole; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D014230:Triazoles; C045575:1,2,4-triazole; D051546:Cyclooxygenase 2
keywords: 1,2,4-Triazole; Anti-inflammatory; Cyclooxygenase selectivity; Docking study; Ulcerogenicity