CoMFA on the melanogenesis inhibitory activity of alkyl-3,4-dihydroxybenzoate, N-alkyl-3,4-dihydroxybenzamide analogues, and prediction of higher active compounds.
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).
Kim
Sang-Jin
SJ
Department of Cosmetic Science, Daejeon Health Sciences College, Gayang 2-dong, Dong-gu, Daejeon, 300-711, Korea.
Myung
Pyung-Keun
PK
Sung
Nack-Do
ND
D000465:Algorithms; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D062385:Hydroxybenzoates / Q000737:chemistry* / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship
D001549:Benzamides; D062385:Hydroxybenzoates; D008543:Melanins