In silico approach in the development of structural analogues of resveratrol with improved distribution in the central nervous system

Abstract

Resveratrol exerts neuroprotective effects that are not only due to anti-inflammatory and antioxidant activity but also by launched biogenesis via sirtuin-1 (SIRT1) protein that protects cells from oxidative stress. Resveratrol has low bioavailability due to low aqueous solubility and rapid metabolism. To improve the pharmacological profile, one of the strategies is the structural modification and selecting an analogue that would activate SIRT1 and improve pharmacokinetics. The aim was to examine the neuroprotective potential of resveratrol analogues through the analysis of the binding affinity to the sirtuin-1 receptor and with improved permeability through the blood-brain barrier. 15 of them have a higher affinity for the target. Four analogues are characterized by better properties including both higher permeability and higher binding affinity for SIRT1 compared to resveratrol. The selected compounds are assumed to have better bioavailability and CNS distribution, and further studies are proposed to confirm their effects and use as neuroprotective agents.