Molecular modeling, enzyme activity, anti-inflammatory and antiarthritic activities of newly synthesized quinazoline derivatives

Abstract

Aim: 16 thioxoquinazolines were evaluated in vivo for anti-inflammatory activity using carrageenan-induced paw edema assay. Results: In particular, out of the targets (1–16), compounds 4 and 6 displayed the highest anti-inflammatory activity (≥80%) and furtherly tested against complete Freund’s adjuvant-induced arthritic rats. Significant reduction in the serum level of IL-1β, COX-2 and prostaglandin E2 in the complete Freund’s adjuvant rats is demonstrated by compounds 4 and 6. Furthermore, compound 4 showed non-selective activity against COX-1 and COX 2, however, compound 6 was specific toward COX-2. Molecular docking study has demonstrated the possible binding modes of the active quinazolines 4 and 6 in the COX-2 active site. Conclusion: These targets could be used as templates for further development of new derivatives with potent anti-inflammatory activity.