Neomangiferin, a Naturally Occurring Mangiferin Congener, Inhibits Sodium-Glucose Co-transporter-2: An In silico Approach.

Type 2 diabetes is a major health concern contributing to most of diabetic cases worldwide. Mangiferin and its congeners are known for their diverse pharmacological properties. This study sought to investigate the inhibitory property of naturally occurring mangiferin congeners on sodium-glucose co-transporter 2 protein (SGLT-2) using comprehensive computational methods. The naturally occurring mangiferin congeners were subjected to molecular docking, molecular dynamics (MDs) simulation (100 ns), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy, density functional theory calculations (B3LYP 6-31G basis set), and ADMET approaches to identify potential SGLT-2 inhibitor. The molecular docking studies revealed neomangiferin (-9.0 kcal/mol) as the hit molecule compared with dapagliflozin (-8.3 kcal/mol). Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) plots from the MD simulations established that neomangiferin stabilizes SGLT-2 better than the dapagliflozin, a standard drug. The MM-PBSA binding free energy calculations showed that neomangiferin (-26.05 kcal/mol) elicited better binding affinity than dapagliflozin (-17.42 kcal/mol). The electronic studies showed that neomangiferin (3.48 eV) elicited high electrophilicity index compared with mangiferin (3.31 eV) and dapagliflozin (2.11 eV). Also, the ADMET properties showed that the hit molecule is safe when administered to diabetic subjects. The current in silico studies suggest that neomangiferin could emerge as a promising lead molecule as a SGLT-2 inhibitor.

Revealing the Acetylcholinesterase Inhibitory Potential of Phyllanthus amarus and Its Phytoconstituents: In Vitro and in Silico Approach.

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, ß-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.