Computational Studies on Carbazole-Pyranocoumarin Conjugate Against α-glucosidase Enzyme
Abstract
α-Glucosidase is an enzyme responsible for releasing the α-D-glucose monomer through hydrolysis reactions. The release of this monomer increases the sugar concentration in the blood and increases the risk of type-2 diabetes mellitus (DM) patients. Through computational studies, we evaluate the structural and inhibitory efficiency of the new carbazole-pyranocoumarin conjugate/Carbazomarin-C as α-Glucosidase inhibitor at the molecular level. We found that Carbazomarin-C (Car) has promising drug-likeness and ADMET properties. Meanwhile, proton chemical shift modeling through a density functional theory (DFT) approach shows that the Car molecule had an agreement with experimental results. Molecular dynamics simulation was applied to understand their inhibitory efficiency through free energy binding (∆Gbind and ∆Gexp). The results showed that Car (∆Gbind: -6.10 kcal/mol and ∆Gexp: -5.02 kcal/mol) had better inhibition than Acarbose as a control (∆Gbind: -4.48 kcal/mol and ∆Gexp: -3.17 kcal/mol). Moreover, nine residues were responsible for the bond stabilization of both inhibitors, namely F175, R210, V213, Q276, F300, P309, L310, R439, and R443. The information in this work demonstrated how potential Carbazomarin-C is as an α-Glucosidase inhibitor at the molecular level.