SYNTHESIS, ANALGESIC, ANTI-INFLAMMATORY AND MOLECULAR DOCKING STUDIES OF NEW QUINAZOLIN-4-ONE DERIVATIVES

Two new quinazolin-4-one derivatives were synthesized by condensation reaction of 2-phenylbenzoxazin-4-ones and p-aminobenzenesulfonamides, in a medium of acid catalyst and strong polar aprotic solvents (DMSO or DMFA). The compounds are also tested for their yields obtained, by using some of strong polar aprotic solvents and have been investigated for analgesic, anti-inflammatory (in vivo) and in silico docking studies to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzyme COX-2 using Autodock Vina software. The results showed that the investigated compounds (A and C) have a high analgesic and antiinflammatory activities. The compounds A and C showed appreciable inhibition of the edema size with a percent inhibition of 19% and 43% respectively, the anti-inflammatory activity of the compounds showed excellent protection against in comparison with diclofenac sodium that exhibited a significant anti-inflammatory activity with 15% of inhibition, while the analgesic activity was significantly increased after treatment by the both A and C compounds compared with the standard diclofenac sodium. The docking study of compound A and C showed that their score of affinity was found around -8.2 and -9.1 respectively in comparing to diclofenac with -8.4. We concluded that the new synthesized quinazolin-4-one derivatives exhibited anti-inflammatory activity and possess potent analgesic effect; the docking study of the synthesized derivatives confirmed the results and revealed that compounds A, has a significant anti-inflammatory activit