The H+/K+-ATPase or proton pump is a magnesium-dependant enzyme which causes the exchange of a proton against a potassium ion through a membrane. Over activity of this enzyme causes hyperacidity by producing more of hydrochloric acid inside the stomach. This enzyme, therefore, has been found to be a good target for designing compounds to treat hyperacidity. A quantitative structure-activity relationship (QSAR) study has been made on a novel series of biaryl imidazole derivatives acting as H+/K+-ATPase inhibitors. The H+/K+-ATPase inhibition activity of these compounds is found to be significantly correlated with global topological charge indices (GTCIs) and the total polar surface area (TPSA) of the molecules, indicating the involvement of strong electronic interaction between the molecule and the receptor. Based on the correlations obtained, some new H+/K+-ATPase inhibitors are predicted. The docking studies of these predicted compounds exhibit that these compounds will have even better interaction with the receptor than those already marketed. Thus, they can prove more potent drugs for the treatment of hyperacidity.
A quantitative structure-activity relationship (QSAR) and molecular docking study has been performed on a series of heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine derivatives acting as acid pump antagonists in order to have a better understanding of the mechanism of H+/K+-ATPase inhibition. The QSAR study shows a significant correlation of activity with Global Topological Charge Indices (GTCI) of the compounds and the hydrophobic constant π of some substituents, indicating that the charge transfer within the molecule and the hydrophobic property of some substituents will be the controlling factor of the activity of these compounds and that there can be dispersion interaction between the molecules and the receptor, where some substituents may have hydrophobic interaction, too. Based on this correlation some new compounds with higher potency have been predicted and their docking study has been performed to see if they can have better interaction with the receptor. The ADME properties of these predicted compounds have also been reported that follow Lipinski's rule of five.
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