Document Report Card

Basic Information

ID: ALA4715740

Journal: Eur J Med Chem

Title: Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibitory activities and molecular docking studies of substituted 2-mercapto-4(3H)-quinazolinones.

Authors: Abdel-Aziz AA,Abou-Zeid LA,ElTahir KEH,Ayyad RR,El-Sayed MA,El-Azab AS

Abstract: A new series of 2-substituted mercapto-4(3H)-quinazolinone 1-26 were synthesized and assessed for in vivo anti-inflammatory and analgesic activities and in vitro inhibition of cyclooxygenase COX-1/COX-2. A new series of 2-substituted mercapto-4(3H)-quinazolinone 1-26 were synthesized and assessed for in vivo anti-inflammatory and analgesic activities. The potent anti-inflammatory compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. Compounds 1, 3, 5, 11, 12, 13, 15, 17, and 25 exhibited potent anti-inflammatory effects, with half-maximal effective dose (ED50) values of 65.7-102.4 mg/kg, (0.16-0.36 mmol/kg), and strong analgesic activities, with ED50 values of 33.3-104.6 mg/kg, (0.07-0.34 mmol/kg). These values were compared with those of diclofenac sodium [ED50 values: 112.2 and 100.4 mg/kg, (0.35 and 0.31 mmol/kg)], and celecoxib [ED50 values: 84.3 and 71.6 mg/kg (0.22 and 0.19 mmol/kg)], respectively as reference drugs. Compounds 1, 11, 12, 13, 15, 17, and 25 exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC50) values of 0.70-2.0 μM and selectivity index (SI) values of more than 50-142.9 compared with celecoxib as reference drugs (IC50 = 0.30 μM and COX-2 SI: >333). Potent COX-2 inhibitors, i.e., compounds 15, 11, and 17 were docked into the binding site pockets of COX-1 and COX-2. These compounds exhibited strong interactions at the COX-2 binding site and poor interactions at COX-1 active site pocket.

CiteXplore: 27318118

DOI: 10.1016/j.ejmech.2016.05.066