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Synthesis And Inhibitory Effect Of Kojic Acid Derivatives On Tyrosinase

Posted on:2016-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:P YangFull Text:PDF
GTID:2191330479494185Subject:Applied Chemistry
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Tyrosinase is a kind of metal enzyme containing dinuclear copper ions and a key rate-limiting enzyme to restrict the synthesis of melanin. Kojic acid is a product isolated from aerobic fermentative products of fungus, used as an anti-tyrosinase agent. Parts of its derivatives have been applied in cosmetic market. However, kojic acid is sensitive to themal and easy to be oxidized. So, it is a hot topic to find more stable and effective kojic acid derivatives.In this paper, kojic acid being used as a strated material, several kinds of kojic acid metal complexes were synthesized through coordination reaction, which contained the ions of Fe(III), Zn(II), Mn(II) and Cu(II). Monophenolase inhibition, odiphenolase inhibition and inhibition type were examined. Results indicated that three kinds of kojic acid metal complexes improved their tyrosinase inhibition obviously except for KA-Cu(II)(3d). It meant that the introduction of these metal ions enhanced the tyrosinase inhibition activity of Kojic acid. Among these compounds, KA-Zn(II)(3b) was the strongest inhibitor and its IC50 value was 18μM, which was of 4 times of kojic acid. Enzyme kinetics shown that all of them were noncompetitive inhibitors.As the same, kojic acid being acted as a strated material, several kinds of kojic acid-amino acid Mannich bases were synthesized through Mannich reaction. However, no enzyme dynamic test was conducted for KA-Met(4e) and KA-Cys(4f) because the yield of them were too low and the purification process were difficult. For the other four kinds of kojic acid-amino acid Mannnich derivatives, their inhibition on monophenolase and odiphenolase tyrosinase were significantly improved. It meant that the introduction of amino acid enhanced the tyrosinase inhibition activity of Kojic acid. Among these compounds, KA-Tau(4d) was the strongest inhibitor, which was 7 time of kojic acid, and its IC50 value was 10μM. Enzyme kinetics shown that all of them were competitive inhibitors which were different from that of kojic acid. It was speculated that as the introduction of amino acid, kojic acid-amino acid Mannich bases had the similar structure with L-dopa which was used as the substrate in tyrosinase activity assay. So these inhibitors could compete the copper sites of tyrosinase with L-dopa, inhibiting the generation of intermediate between enzyme and substrate.On this basis, KA-Gly being used as a started material due to its excellent yield, several kinds of kojic acid glycine Mannich base metal complexes were synthesized through coordination reaction. Monophenolase inhibition were examined. Results indicated that only two compounds’ tyrosinase inhibition were slightly improved than KA-Gly, which were(KA-Gly)-Zn(II)(5a) and(KA-Gly)-Fe(III)(5b). It meant that the introduction of metal ions had the less effect on the tyrosinase inhibition activity of Kojic acid glycine Mannich base.Structures of all the intermediates and final compounds were respectively confirmed by 13 C NMR, 1H NMR, IR, UV, MS or TG.
Keywords/Search Tags:kojic acid, amino acid, metal complexes, tyrosinase inhibition
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