A theoretical antioxidant pharmacophore for resveratrol.

The structure-activity relationship has been used to study the determination of antioxidant pharmacophore for resveratrol using quantum chemistry calculations by the Functional of Density Theory method. According to the geometry obtained by using a B3LYP/6-31G(*), the HOMO, ionization potential, bond dissociation energies, stabilization energies, and spin density distribution, the electron or hydrogen abstraction in para position is more favored than in meta positions for resveratrol and related derivatives because of the resonance effects. Comparison with structurally related compounds revealed that the antioxidant pharmacophore of resveratrol is 4-hydroxystilbene. Spin distribution showed that the pi-type electron system determines the stability of radicals and the unpaired electrons are mainly distributed to the O-atom in para position, double bond, and B-benzene ring. The antioxidant activity of resveratrol is related to the stabilization energy of 4-hydroxystilbene in resveratrol hydroxylated derivatives. Furthermore, the results explain the activity difference between resveratrol and its hydroxylated derivatives.