Abstract
In the present study, new Schiff’s base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents.
Highlights
IntroductionFungi, plants and keratinocytes of skin and hair of animals, catalyzed by tyrosinase, made the surface coloring, which played an important role in protecting the skin and eye from ultraviolet radiation and preventing overheat of internal organization
Melanin existed in bacteria, fungi, plants and keratinocytes of skin and hair of animals, catalyzed by tyrosinase, made the surface coloring, which played an important role in protecting the skin and eye from ultraviolet radiation and preventing overheat of internal organizationPLOS ONE | DOI:10.1371/journal.pone.0138578 September 30, 2015Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics
This article reported the synthesis of tyrosinase inhibitors and screening on monophenolase and diphenolase of tyrosinase, tested the inhibitory types, mechanisms, fluorescence quenching, copper ions interaction, molecular simulation to further unravel the mechanisms, and its oxidation resistance as a supplement of biological activity
Summary
Fungi, plants and keratinocytes of skin and hair of animals, catalyzed by tyrosinase, made the surface coloring, which played an important role in protecting the skin and eye from ultraviolet radiation and preventing overheat of internal organization. Hydroquinone, kojic acid, azelaic acid, and arbutin as tyrosinase inhibitors have been applied in pharmaceuticals and cosmetics [12,13,14,15]. Safe and efficient tyrosinase inhibitors will provid theoretical basis for the treatment of pigment disorders and enrich whitening cosmetics markets [19,20]. Because N and S atoms of the compounds played a key role in the coordination of metals at the active site of metalloprotein [28], they may have the ability to chelate the copper ions in active center of tyrosinase. The results could provide references for developing tyrosinase inhibitor as addition agent for use in fields of whitening cosmetics or fruit and vegetable preservation
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