Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens
up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol,
particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved
pharmacokinetic properties and higher binding affinities towards PPAR-γ.
Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure
was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software.
Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+
Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to
docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having
higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor,
23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy
stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ.
These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable
and wider distributed in body than resveratrol.
Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug
development. Although experimental validation of obtained in silico results is required, this work can be considered
as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.