Department of Chemistry, Nanchang University, Nanchang 330031, PR China.
Department of Chemistry, Nanchang University, Nanchang 330031, PR China; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, PR China.
Int J Biol Macromol. 2017 Oct;103:1096-1106. doi: 10.1016/j.ijbiomac.2017.05.036. Epub 2017 May 10.
Novel Tyrosinase Inhibitors of 4-functionalized Thiophene-2-carbaldehyde thiosemicarbazone (TCT) derivatives (1-8) had been synthesized and Spectrofluorimetry, H and C NMR titration and Molecular docking had been used to investigate their inhibitory activities and mechanisms on tyrosinase. The results showed that the inter-molecular interactions or hydrogen bond formation by increasing length of carbon chain or introducing benzene ring to the 4-functionalized ester group promoted or stabilized formation of complexes between modifier and tyrosinase, and enhanced the inhibitory activity of modifiers. The inhibitory activity of 4-benzoy methoxy-TCT was much stronger than that of any other synthesized tested modifiers, which was well explained by molecular docking and further verified by spectrofluorimetry and NMR titration by assuming that there existed an inter-molecular interaction besides formation of hydrogen bonds between the amino acid residues ASN260, GLU256, HIS85 of enzyme and the modifier.We concluded that 4-benzoy methoxy substitution of TCT was a good route obtaining novel tyrosinase inhibitors and deserved further studies.
新型酪氨酸酶抑制剂 4-功能化噻吩-2-甲醛缩氨硫脲（TCT）衍生物（1-8）已经被合成，利用荧光光谱法、H 和 C NMR 滴定和分子对接研究了它们对酪氨酸酶的抑制活性和作用机制。结果表明，通过增加碳链长度或在 4-功能化酯基中引入苯环，增加分子间相互作用或氢键形成，促进或稳定修饰剂与酪氨酸酶之间的配合物形成，从而增强修饰剂的抑制活性。4-苯甲酰甲氧基-TCT 的抑制活性远强于其他任何合成的测试修饰剂，这通过分子对接得到了很好的解释，并通过假设除了形成氢键外，在酶的氨基酸残基 ASN260、GLU256、HIS85 与修饰剂之间还存在分子间相互作用，通过荧光光谱法和 NMR 滴定得到了进一步验证。我们得出结论，TCT 的 4-苯甲酰甲氧基取代是获得新型酪氨酸酶抑制剂的良好途径，值得进一步研究。
