Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

Abstract

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Discovery of Novel and Selective Schiff Base Inhibitors as a Key for Drug Synthesis, Molecular Docking, and Pharmacological Evaluation

“…Initially, the cocrystallized acarbose obtained by using the proteins was subsequently isolated as an independent molecule and used as the control. The software program known as Molecular Operating Environment (MOE) 2019 , was employed here; this software gained remarkable attention for the preparation of compounds into proteins . Subsequently, at pH 7, hydrogen atoms were employed for obtaining the structure while water molecules were removed by applying the QuickPrep option available in the tool bar of MOE.…”

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide–hydrazone derivatives of 3,4-dihydroxyphenylacetic acid

“…Notably, numerous pieces of evidences indicate that α-glucosidase inhibitors may prove beneficial in the treatment of carbohydrate-mediated diseases, including conditions such as cancer, Alzheimer’s disease, hepatitis, and bacterial and viral infections 20 – 22 . Consequently use of α-glucosidase inhibitors has emerged as a promising therapeutic avenue for mitigating the risks associated with diabetes and related conditions 23 , 24 . Therefore, the pursuit of designing and developing novel α-glucosidase inhibitors with high efficacy and minimal side effects holds a great appeal for medicinal chemists.…”