虚拟筛选技术在黑色素生成抑制剂研发中的应用

doi:10.3969/j.issn.2097-2806.2024.06.013

摘要/Abstract

摘要：

黑色素含量水平及其分布被认为是影响肤色的重要因素。在黑色素生成过程中，酪氨酸酶（TYR）是调节黑色素含量的关键限速酶。小眼畸形相关转录因子（MITF）是黑色素细胞的主要调控因子，在黑色素细胞的分化和增殖中发挥着关键作用。大量研究表明通过降低TYR活性或稳定性，或干扰MITF正常转录，可预防或缓解黑色素生成异常而产生的各种皮肤问题。虚拟筛选具有成本低、效率高的优点，该技术应用于筛选黑色素生成抑制剂的研究具有良好的应用前景。本文总结了黑色素的合成和调控规律，综述了虚拟筛选技术在黑色素生成抑制剂研发中的应用进展，为探索黑色素生成抑制剂先导化合物提供参考。

关键词: 黑色素抑制剂, 酪氨酸酶, 小眼畸形转录因子, 虚拟筛选

Abstract:

With the development of economy and society, great business opportunities have emerged in the skin whitening and anti-spot industry. Melanin content and its distribution are considered to be important factors affecting skin color. Tyrosinase （TYR） is a key rate-limiting enzyme in the regulation of melanin content. Microphthalmia-associated transcription factor （MITF） is a major regulator of melanocytes and plays a key role in the differentiation and proliferation of melanocytes. A large number of studies have shown that by reducing the activity or stability of TYR, or interfering with the normal transcription of MITF, various skin problems caused by abnormal melanin production can be prevented or alleviated. Virtual screening has the advantages of low cost and high efficiency. This technology has a good application prospect in screening melanin synthesis inhibitors. In this paper, the synthesis and regulation of melanin were summarized, and the application progress of virtual screening technology in the development of melanin production inhibitors was reviewed, which provided a reference for exploring the lead compounds of melanin production inhibitors.

Key words: melanin inhibitors, tyrosinase, microphthalmia-associated transcription factor, virtual screening

中图分类号:

TQ658

胡金金, 刘智禹, 陈小娥, 陈贝. 虚拟筛选技术在黑色素生成抑制剂研发中的应用[J]. 日用化学工业（中英文）, 2024, 54(6): 718-726.

Jinjin Hu, Zhiyu Liu, Xiaoe Chen, Bei Chen. Application of virtual screening technology in the development of melanin generation inhibitors[J]. China Surfactant Detergent & Cosmetics, 2024, 54(6): 718-726.

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TYR抑制剂	来源	抑制机理	参考文献
对苯二酚	苯的衍生物	抑制酪氨酸到多巴的转换	[21]
熊果苷	对苯二酚的衍生物	TYR的可逆抑制剂	[22]
曲酸	醋酸杆菌，曲霉菌和青霉菌	金属离子螯合剂	[23]
壬二酸	卵圆糠秕孢子	竞争性TYR抑制剂	[24]
肉桂酸	桂皮	TYR的可逆抑制剂	[25]
香豆素	黑香豆	非竞争性TYR抑制剂	[26]
苯硫脲	硫脲类衍生物	螯合剂，减少TYR表达	[27]

MITF抑制剂	来源	抑制机理	参考文献
光草甘定	甘草	抑制PKA和MAPK信号通路	[29]
NNT	烟酰胺类衍生物	抑制MITF的表达	[30]
乙酰水杨酸	治疗疼痛，发热的药物	降解MITF的蛋白酶	[31]
植物皂苷	高等植物	抑制cAMP和Wnt信号通路	[32]
芦荟发酵提取物	芦荟	减少黑色素生成酶的相关表达	[33]
白芦藜醇	浆果	抑制cAMP信号通路	[34]