ABSTRACT
In this study, we have synthesized and studied de novo tyrosinase inhibitor, MHY1556, which showed significantly better efficacy than other pre-existing tyrosinase inhibitors in vitro experiments. The IC50 value of MHY1556 was 0.50µM which was significantly lower than that of kojic acid (IC50=53.95µM), which is a well-known tyrosinase inhibitor and was used as a positive control in this study. We predicted the tertiary structure of tyrosinase, simulated the docking with compound MHY1556 and confirmed that the compound strongly interacts with mushroom tyrosinase residues. Substitutions with a hydroxy group at both R1 and R3 of the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase, especially through the hydrogen bonding interaction of the hydroxyl group at R1 with GLY281. In addition, MHY1556 showed concentration-dependent inhibitory effects in melanin content assay where B16F10 melanoma cells were treated with α-melanocyte stimulating hormone (α-MSH), and also there is no significant cytotoxicity of this compound in cell viability assay conducted in B16F10 melanoma cells. The tyrosinase activity assay results with MHY1556 also support its potent inhibitory effects. Therefore, our data strongly suggest MHY1556 suppresses the melanogenesis via a tyrosinase inhibitory effect.
Subject(s)
Benzothiazoles/chemical synthesis , Enzyme Inhibitors/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Resorcinols/chemical synthesis , Agaricales/enzymology , Animals , Benzothiazoles/metabolism , Benzothiazoles/toxicity , Binding Sites , Cell Line, Tumor , Cell Survival/drug effects , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/toxicity , Mice , Molecular Docking Simulation , Monophenol Monooxygenase/metabolism , Protein Binding , Protein Structure, Tertiary , Pyrones/chemistry , Pyrones/metabolism , Pyrones/toxicity , Resorcinols/metabolism , Resorcinols/toxicityABSTRACT
We propose a new power-splitting scheme in two-dimensional photonic crystals that can be applicable to photonic integrated circuits. The proposed power-splitting mechanism is analogous to that of conventional three-waveguide directional couplers, utilizing coupling between guided modes supported by line-defect waveguides. Through the analysis of dispersion curve and field patterns of modes, the position in propagation direction, where an input field is split into a two-folded image, is determined by simple mode analysis. Based on the calculated position, a photonic crystal power-splitter is designed and verified by finite-difference timedomain computation.
