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

Abstract

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

CLC Number:

TQ658

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.

Figures/Tables 6

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References 50

[1]	Maranduca M A, Branisteanu D, Serban D N, et al. Synthesis and physiological implications of melanic pigments[J]. Oncology Letters, 2019, 17 (5) : 4183-4187. doi: 10.3892/ol.2019.10071 pmid: 30944614
[2]	Shoichet B K. Virtual screening of chemical libraries[J]. Nature, 2004, 432 (7019) : 862-865.
[3]	Yamaguchi Y, Brenner M, Hearing V J. The regulation of skin pigmentation[J]. Journal of Biological Chemistry, 2007, 282 (38) : 27557-27561. doi: 10.1074/jbc.R700026200 pmid: 17635904
[4]	Hasegawa T. Tyrosinase-expressing neuronal cell line as in vitro model of Parkinson’s disease[J]. International Journal of Molecular Sciences, 2010, 11 (3) : 1082-1089.
[5]	Pillaiyar T, Manickam M, Jung S. Downregulation of melanogenesis: drug discovery and therapeutic options[J]. Drug Discovery Today, 2017, 22 (2) : 282-298. doi: S1359-6446(16)30340-3 pmid: 27693716
[6]	Lai X, Wichers H J, Soler-Lopez M, et al. Structure and function of human tyrosinase and tyrosinase-related proteins[J]. Chemistry, 2018, 24 (1) : 47-55.
[7]	Sanchez-Ferrer A, Rodriguez-Lopez J N, Garcia-Canovas F, et al. Tyrosinase: a comprehensive review of its mechanism[J]. Biochimica Biophysica Acta, 1995, 1247 (1) : 1-11.
[8]	Li J, Feng L, Liu L, et al. Recent advances in the design and discovery of synthetic tyrosinase inhibitors[J]. European Journal of Medicinal Chemistry, 2021.
[9]	Wang Y, Viennet C, Robin S, et al. Precise role of dermal fibroblasts on melanocyte pigmentation[J]. Journal of Dermatological Science, 2017, 88 (2) : 159-166. doi: S0923-1811(17)30082-8 pmid: 28711237
[10]	Xu W, Gong L, Haddad M M, et al. Regulation of microphthalmia-associated transcription factor mitf protein levels by association with the ubiquitin-conjugating enzyme hUBC9[J]. Experimental Cell Research, 2000, 255 (2) : 135-143. pmid: 10694430
[11]	Herraiz C, Garcia-Borron J C, Jimenez-Cervantes C, et al. MC1R signaling. Intracellular partners and pathophysiological implications[J]. Biochimica Biophysica Acta-Molecular Basis of Disease, 2017, 1863 (10) : 2448-2461.
[12]	Azam M S, Kwon M, Choi J, et al. Sargaquinoic acid ameliorates hyperpigmentation through cAMP and ERK-mediated downregulation of MITF in alpha-MSH-stimulated B16F10 cells[J]. Biomed Pharmacother, 2018, 104: 582-589.
[13]	Pillaiyar T, Manickam M, Jung S H. Recent development of signaling pathways inhibitors of melanogenesis[J]. Cellular Signalling, 2017, 40: 99-115. doi: S0898-6568(17)30238-3 pmid: 28911859
[14]	Song Kangkang. The effect of inhibitors on tyrosinase and the regulation of melanin production[D]. Xiamen: Xiamen University, 2007.
[15]	VanGelder C W G, Flurkey W H, Wichers H J. Sequence and structural features of plant and fungal tyrosinases[J]. Phytochemistry, 1997, 45 (7) : 1309-1323. pmid: 9237394
[16]	Roulier B, Peres B, Haudecoeur R. Advances in the design of genuine human tyrosinase inhibitors for targeting melanogenesis and related pigmentations[J]. Journal of Medicinal Chemistry, 2020, 63 (22) : 13428-13443.
[17]	Singh P, Pandey K M. Structural modeling of human tyrosinase protein using computational methods[J]. Biotechnological Research, 2016, 2 (1) : 15-24.
[18]	Matoba Y, Kumagai T, Yamamoto A, et al. Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis[J]. Journal of Biological Chemistry, 2006, 281 (13) : 8981-8990. doi: 10.1074/jbc.M509785200 pmid: 16436386
[19]	Harir M, Bellahcene M, Baratto M C, et al. Isolation and characterization of a novel tyrosinase produced by Sahara soil actinobacteria and immobilization on nylon nanofiber membranes[J]. Journal of Biotechnology, 2018, 265: 54-64. doi: S0168-1656(17)31737-6 pmid: 29133199
[20]	Hsiao N W, Tseng T S, Lee Y C, et al. Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors[J]. Journal of Chemical Information and Modeling, 2014, 54 (11) : 3099-3111.
[21]	Tse T W. Hydroquinone for skin lightening: safety profile, duration of use and when should we stop[J]. Journal of Dermatological Treatment, 2010, 21 (5) : 272-275.
[22]	Wang Xiaoqian. The ups and downs of arbutin-analysis of whitening ingredient arbutin[J]. Chinese Cosmetics, 2019 (10) : 85-87.
[23]	He Min, Fan Meiyan, Yang Wei, et al. Research progress of kojic acid tyrosinase inhibitors[J]. Chemical Reagent, 2022, 44 (7) : 1001-1011.
[24]	Yu J S, Kim A K. Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells[J]. Journal of Biomedical Science, 2010, 17: 1-5.
[25]	Ullah S, Kang D, Lee S, et al. Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells[J]. European Journal of Medicinal Chemistry, 2019, 161: 78-92. doi: S0223-5234(18)30887-0 pmid: 30347330
[26]	Kamauchi H, Kinoshita K, Koyama K. Coumarins with anti-melanogenesis activities from a chemically engineered extract of a marine-derived fungus[J]. Heterocycles, 2018, 96 (2) : 273-285.
[27]	Ujan R, Saeed A, Ashraf S, et al. Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors[J]. Journal of Biomolecular Structure and Dynamics, 2021, 39 (18) : 7035-7043.
[28]	Motiani R K, Tanwar J, Raja D A, et al. STIM1 activation of adenylyl cyclase 6 connects Ca²⁺ and cAMP signaling during melanogenesis[J]. Embo Journal, 2018, 37 (5).
[29]	Pan C, Liu X, Zheng Y, et al. The mechanisms of melanogenesis inhibition by glabrid in: molecular docking, PKA/MITF and MAPK/MITF pathways[J]. Food Science and Human Wellness, 2023, 12 (1) : 212-222.
[30]	Kim B, Lee S, Choi K, et al. N-nicotinoyl tyramine, a novel niacinamide derivative, inhibits melanogenesis by suppressing MITF gene expression[J]. European Journal of Pharmacology, 2015, 764: 1-8. doi: S0014-2999(15)30001-7 pmid: 26118836
[31]	Nishio T, Usami M, Awaji M, et al. Dual effects of acetylsalicylic acid on ERK signaling and MITF transcription leads to inhibition of melanogenesis[J]. Molecular and Cellular Biochemistry, 2016, 412(1-2) : 101-110.
[32]	Villareal M O, Chaochaiphat T, Makbal R, et al. Molecular analysis of the melanogenesis inhibitory effect of saponins-rich fraction of argania spinosa leaves extract[J]. Molecules, 2022, 27 (19) : 6762.
[33]	Jeon G, Ro H S, Kim G R, et al. Enhancement of melanogenic inhibitory effects of the leaf skin extracts of Aloe barbadensis Miller by the fermentation process[J]. Fermentation, 2022, 8 (11) : 580.
[34]	Li Tingting, Zhou Yan, Yin Mingdan, et al. Based on the PKC/CREB/MITF pathway, the effects of resveratrol on the proliferation and melanin synthesis of human melanocytes after ultraviolet irradiation were investigated[J]. Occupation and Health, 2022, 38 (22) : 3054-3060.
[35]	Dhillon A S, Hagan S, Rath O, et al. MAPK kinase signalling pathways in cancer[J]. Oncogene, 2007, 26 (22) : 3279-3290. doi: 10.1038/sj.onc.1210421 pmid: 17496922
[36]	Chen S, Han C, Miao X, et al. Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads[J]. Nat. Commun., 2019, 10 (1): 877. doi: 10.1038/s41467-019-08691-3 pmid: 30787281
[37]	Park S, Morya V K, Nguyen D H, et al. Unrevealing the role of P-protein on melanosome biology and structure, using siRNA-mediated down regulation of OCA2[J]. Mol. Cell Biochem., 2015, 403 (1-2) : 61-71. doi: 10.1007/s11010-015-2337-y pmid: 25656818
[38]	Zhu Jun, Ji Chong, Qiu Jing, et al. Application progress of virtual screening in the discovery of cosmetic efficacy raw materials[J]. Journal of Light Industry, 2023, 38 (1) : 119-126.
[39]	Bagherzadeh K, Talari F S, Sharifi A, et al. A new insight into mushroom tyrosinase inhibitors: docking, pharmacophore-based virtual screening, and molecular modeling studies[J]. Journal of Biomolecular Structure & Dynamics, 2015, 33 (3) : 487-501.
[40]	Choi J, Lee Y M, Jee J G. Thiopurine drugs repositioned as tyrosinase inhibitors[J]. International Journal of Molecular Sciences, 2017, 19 (1) : 77.
[41]	Choi J, Choi K E, Park S J, et al. Ensemble-based virtual screening led to the discovery of new classes of potent tyrosinase inhibitors[J]. Journal of Chemical Information and Modeling, 2016, 56 (2) : 354-367. doi: 10.1021/acs.jcim.5b00484 pmid: 26750991
[42]	Vittorio S, Seidel T, German M P, et al. A Combination of pharmacophore and docking‐based virtual screening to discover new tyrosinase inhibitors[J]. Molecular Informatics, 2020, 39 (3) : 1900054.
[43]	Lim D, Lee K J, Kim Y, et al. A basic domain-derived tripeptide inhibits MITF activity by reducing its binding to the promoter of genes[J]. Journal of Investigative Dermatology, 2021, 141 (10) : 2459-2469.
[44]	Guo D, Lui G Y L, Lai S L, et al. RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes[J]. International Journal of Cancer, 2019, 144 (12) : 3070-3085.
[45]	Joung J Y, Lee H Y, Park J, et al. Identification of novel rab27a/melanophilin blockers by pharmacophore based virtual screening[J]. Applied Biochemistry and Biotechnology, 2014, 172 (4) : 1882-1897.
[46]	Visser M, Kayser M, Grosveld F, et al. Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation[J]. Pigment Cell & Melanoma Research, 2014, 27 (2).
[47]	Morya V K, Dung N H, Singh B K, et al. Homology modelling and virtual screening of P-protein in a quest for novel antimelanogenic agent and In vitro assessments[J]. Experimental Dermatology, 2014, 23 (11) : 838-842. doi: 10.1111/exd.12549 pmid: 25236473
[48]	Li Q, Yang H Y, Mo J, et al. Identification by shape-based virtual screening and evaluation of new tyrosinase inhibitors[J]. PeerJ, 2018, 6: 4206. doi: 10.7717/peerj.4206 pmid: 29383286
[49]	Bo W C, Chen L, Qin D Y, et al. Application of quantitative structure-activity relationship to food-derived peptides: Methods, situations, challenges and prospects[J]. Trends in Food Science & Technology, 2021, 114: 176-188.
[50]	Gao H W. Predicting tyrosinase inhibition by 3D QSAR pharmacophore models and designing potential tyrosinase inhibitors from traditional Chinese medicine database[J]. Phytomedicine, 2018, 38: 145-157. doi: S0944-7113(17)30173-3 pmid: 29425647

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]

Application of virtual screening technology in the development of melanin generation inhibitors

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