Background: Type 2 diabetes mellitus continues to pose a threat to the existence of the human race. The increasing number of diabetic subjects can be effectively controlled by targeting enzymes responsible for high blood glucose levels. Xanthones are a class of phytochemicals that possesses promising pharmacological potentials. Objective: This study identified fructose 1,6-biphosphatase (FBPase) inhibitors by exploring xanthones isolated from African medicinal plants through ensemble docking, molecular dynamics simulation and density functional theory methods. Methods: The study used ensemble docking, molecular dynamics simulation and density functional theory (B3LYP/6-3G (d,p) basis set) and ADMET methods to select lead compound that may be effective as fructose-I,6-biphosphatase inhibitor. Results: The ensemble docking results identified globulixanthone C (-10.0 kcal/mol), 1-Isomangostin (- 9.0 kcal/mol), laurentixanthone A (-9.0 kcal/mol), bangangxanthone A (-8.9 kcal/mol) and staudtiixanthone B (-8.8 kcal/mol) as potential inhibitors of fructose-1,6-biphosphatase. Molecular dynamics studies showed the xanthones established good binding mode and their binding energy ranged from -74.057 to 53.669 kJ/mol. Also, the electronic and ADMET studies of the xanthones elucidated their excellent pharmacological potential. Conclusion: The study identified xanthones as potential fructose-1,6-biphosphatase inhibitors. The ligands' binding energy and MMPBSA calculations supported their possible inhibitory property. Also, the ADMET properties estimated show the ligands as suitable drug candidates as fructose-1,6-biphosphatase inhibitors. Further in vitro and in vivo investigation of the hit molecules is necessary to develop new FBPase inhibitors.
The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of Phyllanthus amarus and its phytoconstituents through an in vitro and in silico approach. The in vitro acetylcholinesterase inhibitory activity of P amarus was carried out, followed by the molecular docking studies of its phytoconstituents. The top-ranked molecules identified through molecular docking were subjected to molecular dynamics simulation (MDS) and density functional theory (DFT) studies. The results obtained revealed the methanolic extract of P amarus as a potent acetylcholinesterase inhibitor, while amarosterol A, hinokinin, β-sitosterol, stigmasterol and ellagic acid were identified as potential acetylcholinesterase inhibitors. The MDS and DFT results are in agreement with those obtained from the docking studies. Our findings suggest further studies on the hit molecules.
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.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
This study aimed at the isolation and characterization of a steroidal compound from the root bark of Uvaria afzelii. The methanolic crude extract of the root bark was suspended in aquous methanol and partitioned with n-hexane to obtain a fraction rich in volatile oils. The n-hexane fraction was subjected to column and preparative thin layer chromatography for isolation and purification of compounds. The n-hexane fraction yielded one steroidal compound. The structure of which was determined by 1H-, 13C- and DEPT135-NMR as campest-5- en-3-ol. The spectroscopic data compared very well with published data.Key words: Extract, Uvaria afzelii, chromatography, campest-5-en-3-ol.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Background of the study This study established the antidiabetic efficacy of Alternantera brasiliana in vitro and in vivo, identified the most active fraction and profiled the chemical constituents of the most active fraction. Methodology The leaf of A. brasiliana was air-dried, pulverized and extracted with methanol and evaluated for its α-amylase activity at different concentrations using in vitro method. The in vivo antidiabetic activity of the extract and glibenclamide was evaluated in glucose loaded and streptozotocin-induced diabetic rats using various doses, while the most active partitioned fraction was identified using glucose loaded method followed by identification of its chemical constituents through GC-MS analysis. Results The extract elicited good α-amylase inhibitory potential with IC 50 = 0.45 mg/mL. Also, the 50 mg/kg dose demonstrated the highest percentage blood glucose level reduction and significantly ( P > 0.05) comparable to glibenclamide (5 mg/kg) from 0.5 to 4 h. The streptozotocin-induced antidiabetic assay showed that the 50 mg/kg demonstrated better activity than glibenclamide (5 mg/kg) and was significantly comparable on days 10 and 14. The aqueous methanol fraction was the most active fraction with 53% blood glucose level reduction at 4 h. The secondary metabolite profiling identified 30 chemical compounds whereby 1H-Indole-2-carboxylic acid, 6-(4-ethoxyphenyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-, isopropyl ester, Benzo[h]quinoline, 2,4-dimethyl-, thymol and 13,5-trioxane as the major constituents. Conclusion The antidiabetic activity demonstrated by the A. brasiliana extract established its antidiabetic efficacy
This study was planned and executed to validate the anti-diabetic ethno-medicinal claim of Caesalpinia pulcherrima (Fabaceae) pods and the isolation of potential chemical compounds responsible for the activity.The anti-diabetic activity of the extract was assayed using oral glucose tolerance test and streptozotocin induced hyperglycaemic rats. The partition fractions of the extract were evaluated for their anti-hyperglycaemic activity using oral glucose tolerance test. The most active fraction was subjected to chromatographic separations that led to the isolation and characterisation of two new polyphenolic compounds. The structures of these compounds were elucidated and characterized using IR, 1D- and 2D-NMR and MS techniques.The extract gave comparable (p>0.05) activity to glibenclamide (5 mg/kg) at 100, 200 and 400 mg/kg at 4 h in oral glucose tolerance test and streptozotocin induced diabetic model on day 21. The most active ethyl acetate fraction (200 mg/kg) elicited comparable activity to the positive control at 0.5-4 h with blood glucose reduction of 52.9 % as compared with glibenclamide (5 mg/kg) of 38.9 % at 4 h. The isolated compounds were identified to be 5-(4-hydroxyphenyl)-3-hydroxy-2-methoxyphenol and 3-(4-methanetriol-2,6-dihydroxyphenyl)-3',4',5',5,7-pentahydroxyflavanonol.The significant anti-diabetic property shown by the pods of C. pulcherrima justified its anti-diabetic ethno-medicinal use and the two new polyphenolic compounds isolated from its most active fraction could have contributed to the observed activity.
Background/Objectives Diabetes mellitus is among the leading cause of death worldwide. This study evaluated the alpha amylase and alpha glucosidase inhibitory properties of kaurane diterpenoids (kauran-13-ol (D1), xylopic acid (D2) and kauran-16α-ol (D3)) from the fruit of X. aethiopica. Methodology In vitro alpha amylase and alpha glucosidase inhibitory assays were performed on D1, D2 and D3 (0.03125, 0.0625, 0.125, 0.25, 0.5, 1.0 and 2.0 mg/mL) and acarbose (0.003125, 0.00625, 0.0125, 0.025, 0.05 and 0.1 mg/mL) followed by molecular docking studies, molecular dynamics simulation and MMPBSA to examine their mode of interaction, binding affinity, binding mode and binding energy established with the enzymes. Also, ADMET properties of the studied diterpenes were examined to explain their druggability potential. Result The in vitro alpha-amylase and alpha-glucosidase studies identified D3 as the most promising inhibitor among the kaurane diterpenes with lower IC 50 values of 0.65 and 0.17 mg/mL. The molecular docking analysis showed that D1, D2 and D3 established vital hydrogen bond, hydrophobic and pi-interaction with the receptors, while the molecular dynamics simulation showed the kaurane diterpenes exhibited good stability at the enzymes’ binding pocket. The MMPBSA binding energy values showed the diterpenes had good binding energies that corroborated that of molecular docking. The ADMET properties identified the compounds as promising drug candidate. Conclusion The study demonstrated that the kaurane diterpenoids have good inhibitory effect on the diabetes enzymes. Further comprehensive investigation into the antidiabetic properties of the diterpenes may lead to the identification of new hit molecule.
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