Molecular Docking and Dynamics Simulations Reveal the Antidiabetic Potential of a Novel Fucoxanthin Derivative from...

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring safer and more effective therapeutic alternatives. This study investigates a novel fucoxanthin derivative isolated from the marine brown alga Chnoospora minima using a comprehensive in silico approach. Molecular docking revealed that the derivative exhibited higher binding affinities toward α-amylase (-9.4 kcal/mol) and α-glucosidase (-8.0 kcal/mol) compared to the reference drug acarbose (-8.5 and -7.4 kcal/mol, respectively). Pharmacokinetic analysis predicted good intestinal absorption and P-gp inhibition (0.894) and moderate plasma clearance (7.864 mL/min/kg), while toxicity predictions classified it in toxicity class 3, with no respiratory or ocular toxicity. Drug-likeness evaluation showed only one Lipinski and one Veber rule violation, common for natural products. Molecular dynamics simulations conducted for 100 ns using NAMD 3.0 confirmed stable protein-ligand complexes with average RMSD values of ~1.3 Å and ~1.8 Å for α-amylase and α-glucosidase, respectively, and consistent hydrogen bonding profiles. Structural analysis identified a substitution of the allene bond with an unsaturated ketone at the C8' position as a key contributor to enhanced enzyme interaction. The findings suggest that this fucoxanthin derivative is a promising natural candidate for T2DM therapy and warrants further investigation through lab experiments (in vitro and in vivo).