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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(01): e1-e8
DOI: 10.1055/s-0041-1742095
Original Article

Discovery of Tyrosinase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

Guan Wang‡   #
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Jin Li‡   #
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Xiao-Li Pan
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Fa-Qian Bu
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Yu-Meng Zhu
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Ao-Xue Wang
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
,
Liang Ouyang
1   State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (Grant No. 81922064, 22177083, 81803755, and 81874290).
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Abstract

Tyrosinase (EC 1.14.18.1) plays an indispensable role in the rate-limiting steps of melanin biosynthesis, and its uncontrolled activity may result in various diseases, such as albinism, melanoma, freckles, etc. The inhibition of tyrosinase activity may provide a useful and efficient strategy to treat hyperpigmentation disorders. However, the widely used tyrosinase inhibitors, like α-arbutin, hydroquinone, and kojic acid, have many shortcomings, such as lower efficacy and much more side effects. Herein, we reported the use of homology modeling and multistep structure-based virtual screening for the discovery of novel tyrosinase inhibitors. In this study, 10 initial potential hits (compounds T1–T10) were evaluated for enzyme inhibition and kinetic study, with kojic acid being used as a control. Among them, the IC50 values of both T1 (11.56 ± 0.98 µmol/L) and T5 (18.36 ± 0.82 µmol/L) were superior to that of kojic acid (23.12 ± 1.26 µmol/L). Moreover, T1 and T5 were also identified as the effective noncompetitive tyrosinase inhibitors by the subsequent kinetic study. Above all, T1 and T5 may represent the promising drug candidates for hyperpigmentation therapy in pharmaceutical fields, as well as the effective whitening agents in cosmetic applications.

Keywords

tyrosinase inhibitors - hyperpigmentation - homology modeling - virtual screening - kinetic study

# These authors contributed equally to this work.




Publication History

Received: 21 October 2021

Accepted: 07 December 2021

Article published online:
02 March 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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