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.
Mixed ligand complexes of Metformin and Isoniazid have been synthesized and characterized by solubility studies, percentage metal analysis, UV-Vis spectroscopy, IR spectroscopy, magnetic moments and conductivity measurements. The infrared spectra revealed the coordination of the ligands to the metal ions [manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)]. Meformin coordinated as a bidentate ligand via the imine nitrogen while isoniazid coordinated through its amino nitrogen (NH) and carbonyl oxygen (C=O). The electronic 2 spectra and magnetic moments for the complexes strongly suggested a six coordinate octahedral geometry. The-1 2-1 molar conductance values of the complexes are within the range 0.45-8.72 Ω cm mol , and this confirms the non-electrolytic nature of the complexes.
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