A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H⁺/K⁺-ATPase Inhibitors

Abstract

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 QSAR model of Olanzapine derivatives as potential inhibitors for 5-HT2A Receptor

“…This study may be identify new compounds through virtual screening and predict the bioactivity of new compounds. The quantitative structure-activity relationship (QSAR) and molecular modeling studies have been increasingly employed in rational drug discovery process to understand the drug receptor interaction and to design new molecules with higher potency [27]. Thus useful clues to designing novel inhibitors of 5-HT2A receptor with high affinity for the treatment of Schizophrenia.…”

Rational Drug Design of Antineoplastic Agents Using 3D-QSAR, Cheminformatic, and Virtual Screening Approaches

“…The developed QSAR models were employed to identify HDAC pharmacophores, optimize HDAC inhibitors and evaluate the inhibitory potency of the novel designed inhibitors [7,66,67]. The CoMFA and CoMSIA 3D-QSAR methodology has been used for development of novel HDAC inhibitors [68][69][70][71][72]. Also, a MIFbased 3D-QSAR approach has been applied on four structurally diverse types of HDAC inhibitors [73].…”

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

“…A series of 179 quinoline and quinazoline heterocyclic analogues exhibiting inhibitory activity against H + /K + -ATPase was investigated by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) by Nayana et al [3] to find that in addition to electrostatic and steric fields, hydrophobic and H-bond donor and acceptor fields were also important for the H + /K + -ATPase inhibition activity of these compounds. Recently, we also found for a series of biarylimidazole derivatives that H + /K + -ATPase inhibition predominantly involves only electronic interaction [19]. …”