Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and-2-alkylsulfonyl-1H-imidazole derivatives


Assadieskandar A. , Amirhamzeh A., Salehi M., Ozadali K., Ostad S. N. , Shafiee A., ...Daha Fazla

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.21, ss.2355-2362, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 21 Konu: 8
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.bmc.2013.01.058
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.2355-2362

Özet

A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. (C) 2013 Elsevier Ltd. All rights reserved.