Journal
MOLECULES
Volume 26, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/molecules26237211
Keywords
glucokinase activators; prenylated flavonoids; molecular docking; molecular dynamics simulation; density functional theory; ADMET
Funding
- Taif University, Taif Saudi Arabia [TURSP-2020/309]
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The study identified potential glucokinase activators from prenylated flavonoids using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. The top-ranked molecules, including arcommunol B, kuwanon S, manuifolin H, and kuwanon F, showed stability at the active site of glucokinase enzyme and were suggested as potential drug-like candidates with glucokinase activating potentials. Further evaluation of these compounds for their in vitro and in vivo effects is recommended.
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.
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