RRC ID 45335
Author Yoshimori A, Oyama T, Takahashi S, Abe H, Kamiya T, Abe T, Tanuma S.
Title Structure-activity relationships of the thujaplicins for inhibition of human tyrosinase.
Journal Bioorg Med Chem
Abstract Tyrosinase inhibitors have become increasingly critical agents in cosmetic, agricultural, and medicinal products. Although a large number of tyrosinase inhibitors have been reported, almost all the inhibitors were unfortunately evaluated by using commercial available mushroom tyrosinase. Here, we examined the inhibitory effects of three isomers of thujaplicin (α, β, and γ) on human tyrosinase and analyzed their binding modes using homology model and docking studies. As the results, γ-thujaplicin was found to strongly inhibit human tyrosinase with the IC50 of 1.15 μM, extremely superior to a well-known tyrosinase inhibitor kojic acid (IC50 = 571.17 μM). MM-GB/SA binding free energy decomposition analyses suggested that the potent inhibitory activity of γ-thujaplicin may be due to the interactions with His367, Ile368, and Val377 (hot spot amino acid residues) in human tyrosinase. Furthermore, the binding mode of α-thujaplicin indicated that Val377 and Ser380 may cause van der Waals clashes with the isopropyl group of α-thujaplicin. These results provide a novel structural insight into the hot spot of human tyrosinase for the specific binding of γ-thujaplicin and a way to optimize not only thujaplicins but also other lead compounds as specific inhibitors for human tyrosinase in a rational manner.
Volume 22(21)
Pages 6193-200
Published 2014-11-1
DOI 10.1016/j.bmc.2014.08.027
PII S0968-0896(14)00614-2
PMID 25288494
MeSH Amino Acid Sequence Enzyme Inhibitors / pharmacology* Humans Molecular Docking Simulation Molecular Sequence Data Monophenol Monooxygenase / antagonists & inhibitors* Monophenol Monooxygenase / chemistry Monophenol Monooxygenase / metabolism Monoterpenes / pharmacology* Sequence Alignment Structure-Activity Relationship Tropolone / analogs & derivatives* Tropolone / pharmacology
IF 3.073
Times Cited 23
Human and Animal Cells G-361(RCB0991)