Structure-activity relationships of polyhydroxystilbene derivatives extracted from Vitis vinifera cell cultures as inhibitors of human platelet aggregation

Several polyhydroxystilbene derivatives obtained from Vitis vinifera cell c ultures were evaluated for in vitro inhibition of human platelet aggregatio n. Computational analyses were performed in an attempt to understand the ph ysico-chemical requirements for antiplatelet activity. A MCMM conformationa l search was conducted using the MM+ force field, and electronic properties were explored with the AM1 method. These compounds exhibited a HOMO charge distribution which is located selectively on the ethylenic bond and the pa ra hydroxylated phenyl ring. However, the energies of the HOMO frontier orb itals do not seem critical to explain the drug-receptor interaction. In con trast, other factors such as the general molecular shape and the lipophilic ity (log Kw) appeared to have more significant effects on biological activi ty.