Molecular Docking Studies of Enzyme Inhibitors and Cytotoxic Chemical Entities

Abstract

Docking is a powerful approach to perform virtual screening on large library of compounds, rank the conformations using a scoring function, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. Using experimentally proven active compounds, detailed docking studies were performed to determine the mechanism of molecular interaction and its binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase-glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homologs, intestinal, and pancreatic maltase, by an average value of~À1.3 and~À0.8 kcal/ mol, respectively. Thirty quinoline derivatives have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty-four analogs, which showed outstanding βglucuronidase activity, have IC 50 values ranging between 2.11 AE 0.05 and 46.14 AE 0.95 μM than standard D-saccharic acid 1,4-lactone (IC 50 = 48.4 AE 1.25 μM). Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. In addition, Small series of morpholine hydrazones synthesized to form morpholine hydrazones scaffold. The in vitro anti-cancer potential of all these compounds were checked against human cancer cell lines such as HepG2 (Human hepatocellular liver carcinoma) and MCF-7 (Human breast adenocarcinoma). Molecular docking studies were also performed to understand the binding interaction.

Ligand Docking Methods to Recognize Allosteric Inhibitors for G-Protein-Coupled Receptors

“…Structural analysis with smaller set of ligands against different proteins has been reported in the literature as well. [27][28][29][30][31][32] We performed docking to check the binding of ligands from GLASS database with GPCRs. We were able to obtain ligands that are reported as targets for particular GPCRs that bind better to the allosteric site as compared to the orthosteric binding site.…”