Quantitative Structure-Activity Relationship and Docking Studies on a series of H+/K+-ATPase inhibitors

Abstract

Background: The Gastric H+/K+-ATPase is also known as proton pump is the enzyme responsible for the acidification of gastric juice. H+/K+ GastroEsophageal Reflux Disease (GERD) and other acid related diseases mainly depend on the inhibition of the gastric H+/K+- ATPase which will finally result in acid secretion in stomach. GERD is one of the diseases that have significant effect on the quality of human life and are the major burden on health care systems is that leads to heart burn, acid regurgitation, chest pain, epigastric pain, and respiratory conditions such as chronic cough. Hence the study of the inhibitors of Gastric H+/K+-ATPase is desired. Methods: Research and online content related to imidazo [1, 2-a]pyrazine and heterocyclic ring analogues (I) that were synthesized and evaluated for their Gastric H+/K+-ATPase inhibitory activity is reviewed, and in order to design and develop still better and more effective H+/K+-ATPase inhibitors, we have made Quantitative Structure Activity Relationship (QSAR), docking and ADMET studies on these compounds. Results: The best MLR equation based on four descriptors along with statistical parameters is obtained using Statistica dataminer software. Using the model expressed by this study we predicted some new compounds of high H+/K+-ATPase inhibition potency. Each predicted compound has very high potency with which only a few compounds of existing series can match. Conclusion: The QSAR and molecular modelling studies suggested that still better compounds can be designed if the flexibility of the molecules can be increased for which attempts can be made to have more saturated atoms in the molecules. Such a compound predicted by us was found to have interactions with the enzyme H+/K+-ATPase almost in the same manner as the FDA approved compounds, lansoprazole, pantaprazole.