Abstract

DOCKING STUDIES OF 4 - (3H)-QUINAZOLINONE DERIVATIVES AS COX-2 INHIBITOR

M. Gnana Ruba Priya*, C. Geetha Priya, Akila E., Savithri T.B. and Kavitha S.K.

ABSTRACT

A series of novel Some 4(3H)-quinazolinone derivatives containing primary aromatic amines were synthesized, characterized and subsequently evaluated for anti inflammatory property. Docking studies with these compounds against cyclooxygenase-2 receptor (PDB 1D: 1PXX) indicated that they exhibit specific interactions with key residues located in the site of the COX-2 structure, which colloborates the hypothesis that these molecules are potential ligands of COX-2. Molecular modeling studies were used to assess the fit of these compounds within the active site of human DHFR. The structural analyses indicate that the coordinate bond interactions, the hydrogen bond interactions, the Vander Waals interactions as well as the hydrophobic interactions between ligand and receptor are responsible simultaneously for the preference of inhibition and potency. In this study, fast flexible docking simulations were performed on quinazolinone derivatives as human COX-2 inhibitors. The results indicated that the quinazolinone ring of the inhibitors forms hydrophobic contacts with Tyr384,Ser529, Arg119 and stacking interaction is conserved in complex with the inhibitor and cofactor .The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, identified 3h,3e and 3f (comparable with standard diclofenac sodium) and the best docking score, indicating effective binding of the compound 3h,3e and 3f at the active site.

Keywords: Anti-inflammatory, Molecular docking, COX-2, 4(3H)-Quinazolinone.