Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Drug and Food Control Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2023 Feb 13;13(1):2578. doi: 10.1038/s41598-023-28852-1.
In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, H-NMR, C-NMR, ESI-MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.
在本研究中，设计并合理合成了一系列芳基取代的硫代喹啉与硫代异氰酸酯缩合而成的化合物。通过红外光谱（IR）、氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、电喷雾质谱（ESI-MS）和元素分析等光谱特征技术确认了目标化合物的形成。在所合成的衍生物中，带有对氯苯基部分的化合物 10g 被证明是最有效的酪氨酸酶抑制剂，IC 值为 25.75 ± 0.19 μM。在动力学研究中，化合物 10g 作为最有效的衍生物，对酪氨酸酶表现出非竞争性抑制模式。此外，还进行了基于计算机的腔检测和分子对接评估，以跟踪 10g 在拟议结合位点内的行为。此外，还测量了 10g 的毒性及其在 A375 细胞系中降低黑色素含量的能力。因此，芳基取代的硫代喹啉与硫代异氰酸酯缩合而成的化合物可能是化妆品、医药和食品工业中酪氨酸酶抑制剂的有前途的候选物。
