Enhanced substituted resorcinol hydrophobicity augments tyrosinase inhibition potency.
The objective of the present study was to investigate to what extent the addition of hydrophobic residues to a 2,4-resorcinol derivative would contribute to their tyrosinase inhibitory potency. Hence, 3-(2,4-dihydroxyphenyl)propionic acid, isolated from Ficus carica, was transformed into esters, and the relationship between the structure of these esters to their mushroom tyrosinase inhibition activity was explored. The enzyme crystallographic structure, published recently (Matoba, Y. et al. J. Biol. Chem. 2006, 281, 8981-8990) was docked with the new esters, and their calculated free energy (FE) and docking energy (DE) were compared with the experimental IC(50) values, providing good correlations. The observed IC(50) of the isopropyl ester was 0.07 microM, and its interaction with the enzyme binding site appears to be composed of four hydrogen bonds and two hydrophobic interactions. It may be concluded that the addition of a hydrophobic moiety to 2,4-resorcinol derivatives augments tyrosinase inhibitory potency as was predicted from the modeling study.
Khatib
Soliman
S
The Laboratory of Natural Medicinal Compounds, MIGAL - Galilee Technology Center, PO Box 831, Kiryat Shmona 11016, Israel.
Nerya
Ohad
O
Musa
Ramadan
R
Tamir
Snait
S
Peter
Tal
T
Vaya
Jacob
J
D001665:Binding Sites; D003300:Copper / Q000378:metabolism; D004952:Esters; D030681:Ficus / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D018515:Plant Leaves / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012118:Resorcinols / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013816:Thermodynamics
C520847:3-(2,4-dihydroxyphenyl)propionic acid; D004952:Esters; D010666:Phenylpropionates; D012118:Resorcinols; D003300:Copper; D014442:Monophenol Monooxygenase