In silico evaluation of antidiabetic potential of selected Uvaria chamae phytochemicals as adenosine monophosphate (AMP)-activated protein kinase modulators
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Abstract
Type 2 diabetes mellitus (T2DM) remains a major global health challenge characterised by impaired glucose and lipid metabolism. Activation of AMP-activated protein kinase (AMPK), a central regulator of cellular energy homeostasis, offers a promising therapeutic strategy for improving insulin sensitivity and metabolic balance. This study employed an in silico approach to evaluate selected phytochemicals from Uvaria chamae, including chamanetin, dichamanetin, uvaretin, isouvaretin, isochamanetin, pinocembrin, and linalool, for their potential as AMPK modulators. The compounds were assessed for physicochemical properties, drug-likeness, pharmacokinetics, and toxicity using SwissADME and ProTox-II, while molecular docking against the AMPK catalytic domain (PDB ID: 4CFF) was done using AutoDock Vina. All phytochemicals adhered to drug-likeness criteria and exhibited good oral bioavailability, with no structural alerts. Docking results revealed strong predicted binding affinities, ranging from -5.2 to -9.5 kcal/mol, compared with metformin (-4.5 kcal/mol). Chamanetin and dichamanetin showed the most favourable interactions with key residues within the AMPK ATP-binding pocket, suggesting potential as lead scaffolds for direct AMPK modulation. These findings provide molecular insight supporting the traditional use of Uvaria chamae in diabetes management and justify further biochemical and pharmacological validation of its active constituents.
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