Discovery of Novel Alanine Aminotransferase and Aspartate Aminotransferase Inhibitors by Large Scales Docking-Based Virtual Screening Publisher



Hosseini FS¹ ; Kazemzadeh H¹ ; Shahsavari P¹ ; Gholami M¹ ; Omrany ZB¹ ; Amanlou A² ; Amanlou M^{1, 2} Show Affiliations
Source: Biointerface Research in Applied Chemistry Published:2023

Abstract

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is the cardinal enzymes in the liver and play a substantial role in balancing many metabolic pathways. A peccadillo, in the activity of these enzymes, can end up in uncontrollable challenges like chronic conditions. Therefore, the demand to use small molecules to control the enzyme's activity and prevent the mentioned challenges will be undeniable in the future. To answer this demand, a large scales virtual screening procedure, using molecular docking of 9127 FDA and world-approved drugs, including herbal medicine, was performed using Autodock 4.2 over the crystal structures of ALT and AST (PDB ID: 7AAT, 3IHJ respectively). The results revealed that small molecule xanthurenic acid-β-glucoside with quinoline monocarboxylic acid backbone and glucoside substitution could fit well in both active sites of ALT and AST and interact properly with the most key residues. These features, accompanied by suitable ADME properties, lower toxicity than previously reported inhibitors, and neoteric general backbone, make them potential candidates that can be used either as medicine in clinical trials or as a structural basis for designing other novel inhibitors. © 2022 by the authors.