Computer-Aided Screening of the Binding Affinities of Some Anti-Diabetic Ligands Obtained from Annona muricata Linn. (Soursop) and their Derivatives against Alpha-glucosidase

Abstract

BackgroundDelaying glucose absorption into the blood – post-prandial – after food intake can play a major ameliorative role in the lifestyle and economic advantage of diabetic (DM) patients, making type 2 diabetes (T2DM), unlike type 1 (T1DM), considerably more, manageable, curable, and preventable. Identifying plant-based lead compounds that will offer much more precise and potent anti-DM activities, with lesser side effects is beneficial. MethodIn this experiment, virtual investigations were done to study the binding properties of some phytoconstituents of Annona muricata (annonaceous acetogenin and flavonoids) and their analogues, against α-glucosidase, to identify possible variations of binding affinities with changes in side-chain moieties, modification of carbon-skeleton through increased cyclisation, side-chain hydroxylation, steric-distortion of the beta-lactone ring of acetogenins, the effect of the introduction of glycoside side-chain moiety. ResultsThe acetogenins and naringenin analogues, pentahydroxy flavanone (-10.40 Kcal/mole), floro-tetrahydroxyflavan (-10.20 Kcal/mole), tetrahydroxyflavan (-10.00 Kcal/mole), naringenin (-09.40 Kcal/mole), naringenin analogue (-09.20 Kcal/mole), as well as, 15 – acetyl – guanacone – 3 (-9.20 Kcal/mole), recorded relatively high binding energies, suggesting that they bonded better as inhibitors, compared to the other compounds, and the standards, metformin (-4.60 Kcal/mole), except acarbose (-9.70 Kcal/mole). The observed major amino acid residues targeted for bonding by the ligands ranged between Arg422, Asn424, Tyr425, and Arg426. ConclusionIt was, however, observed that the addition of glycoside moiety, increasing the number of hydroxyl groups and rings within the carbon-carbon chain (which ultimately generates constitutional isomers) of α-glucosidase inhibitors could further increase their inhibitory potentials against their binding site.