This study aimed to identify novel α-amylase and α-glucosidase inhibitors from Nigerian antidiabetic plants through in silico approach. Virtual screening of the 93 phytoconstituents was performed, and their inhibitory potentials were ranked based on their docking scores. Five hit molecules were selected for each enzyme target with their hydrogen bonding, hydrophobic, electrostatic, and pi interactions analyzed with discovery studio visualizer. The drug-likeness and ADMET studies of the hit molecules were performed to ascertain their druggability properties. Further, three top-ranked hit molecules were subjected to molecular dynamics simulations. The virtual screening, drug-likeness property, and ADMET studies, and molecular dynamics simulations carried out reveal Newbouldiaquinone A, Foetidin, Chamuvaritin, Cajaflavanone, and Azadirolic acid as potential inhibitors of α-amylase while Chamuvaritin, Newbouldiaquinone A, Flowerone, Scoparic acid A and Nimonol were potential inhibitors of α-glucosidase enzyme. Communicated by Ramaswamy H. Sarma

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.

Type 2 diabetes accounts for the largest percentage of all diabetic cases worldwide. Cucurbitane-type triterpenes are mainly found in Momordica charantia and possess excellent pharmacological activities. This study was designed to identify cucurbitane-type triterpene from Momordica charantia using Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, examine its anti-diabetic property with molecular docking against diabetes enzymes (alpha-amylase, alpha-glucosidase, dipeptidyl dipeptidase IV and peroxisome proliferator-activated receptor gamma). The stability and interactions of the docked complexes were investigated using molecular dynamics simulation, while the pharmacokinetic and toxicity profile of the ligand was examined using an ADMET server. (23E)-Cucurbita-5,23,25-triene-3,7-dione (CUB) was identified from the LC-MS profiling of the methanolic extract of M. charantia. The molecular docking studies showed that the identified phytochemical elicited good binding energy against all the target receptors. The RMSD and RMSF plots obtained from the 100 ns molecular dynamics simulation showed that the ligand was stable and established substantial interactions with the amino acid residues of the diabetes enzymes which were confirmed by the MM\GBSA computations. The pharmacokinetic and toxicity properties of the ligand showed it was safer as an anti-diabetic drug candidate. Extensive isolation, in vitro and in vivo studies of the ligand against the diabetic enzymes is recommended.

Diabetes mellitus is a life-threatening non-communicable disease that affects all age groups. Despite the increased attention it has received in recent years, the number of diabetic patients has grown exponentially. These increased cases are attributed to essential enzymes involved in blood glucose regulation. In this study, we attempt to reveal the aldose reductase inhibitory potential of xanthones isolated from African medicinal plants. Ensemble docking, molecular dynamics simulation, density functional theory (DFT), and ADMET methods were employed to identify drug candidates as aldose reductase inhibitors. The ensemble docking results identified mangostenone B, bangangxanthone A, smeathxanthone B, mangostenone A, and allanxanthone B as potent inhibitors against the aldose reductase enzyme. Molecular dynamics studies showed the xanthones established better binding mode and affinities against the enzyme. Moreover, the electronic properties of the xanthones explained their good pharmacological potentials. Therefore, our findings suggest that the hit molecules be investigated in vitro and in vivo for drug development against aldose reductase.