Molecular docking and quantitative structure-activity relationship study of anti-ulcer activity of quinazolinone derivatives

Abstract

Proton pump inhibitors portray the first choice for treating various ulcer diseases because it inhibits H+/K+-ATPase enzyme, by covalently binding to a cysteine residue of either potassium or proton pump, therefore this enzyme is a validated target for anti-ulcer drugs. A Quantitative structure-affinity relationship (QSAR) and molecular docking analysis were carryout on 30 quinazolinone derivatives as H+/K+-ATPase inhibitors. QSAR study was performed using Material studio software version 8.0, while molecular docking analysis of all the novel quinazolinone derivatives was performed using Autodock vina version 4.0 of Pyrx software. The QSAR result reveal a strong correlation value of R2 = 0.9131, R2adj = 0.8914, Q2LOO = 0.8038 and R2 pred = 0.8946 which showed a highly predictive and statistically significant model. Molecular docking analysis revealed that the ligand 25 bind tightly deep to H+/K+-ATPase (protein target). Because of the high binding affinity of −9.3 kcal/mol. This research has revealed a significant correlation between binding score and biological activities of the molecules, and the results are even better than the one proposed by other authors, more also, both results of quantitative structure-affinity relationship (QSAR) and docking studies agree with each other which give chance for design and synthesis of novel anti-ulcer agents exhibiting good action against the receptor (H+/K+-ATPase) Furthermore, the present study prove more potent drugs than the ones already marketed. Keywords: K+/H+-ATPase, GFA, PUD QSAR, DFT, (B3LYP/6-31G∗)