CoMFA on the melanogenesis inhibitory activity of alkyl-3,4-dihydroxybenzoate, N-alkyl-3,4-dihydroxybenzamide analogues, and prediction of higher active compounds.

摘要

To predict a new materials of superior melanogenesis inhibitory activities (MIA), the comparative molecular field analysis (CoMFA) models on MIA of alkyl-3,4-dihydroxybenzoates and N-alkyl-3,4-dihydroxybenzamides analogues against mouse melanoma cell were derived and discussed quantitatively. The optimized CoMFA model II from the field fit alignment demonstrated better predictability of molecular structure with the non-cross validated conventional coefficient (r2 (nev.)=0.984) and cross-validated coefficient (r2 (cv.) or q=0.706) than that from atom based fit alignment. Also, the relative contribution of the optimized CoMFA model II showed the steric (63.8%), electrostatic (18.4%), and hydrophobic (ClogP) field (17.8%), respectively. The results indicated that the esters (alkyl-3,4-dihydroxybenzoates) are more active inhibitors than the amides (N-alkyl-3,4-dihydroxybenzamides). Furthermore, the optimized CoMFA model II is proven to be a useful approach to design a highly active melanogenesis inhibitor molecules, and enables to predict R1 = n-dodecy and R2 = n-heptyloxy substituted compound of alkyl-3,4-dihydroxybenzoates as the most active compounds (Pred. pI50 = 5.87).