Identification by shape-based virtual screening and evaluation of new tyrosinase inhibitors

PeerJ

Yuan Sun¹  Chen Kang²  Qi Li³  Hongyu Yang³  Haopeng Sun³  Jun Mo³  Yue Wu⁴  Yao Chen⁵ 

[1] Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA,United States of America;Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA,United States of America;Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China;Nanjing Duoyuan Biochemistry Co., Ltd., Nanjing, China;School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China;

关键词: Tyrosinase inhibitor;    Molecular shape;    Hit identification;   

DOI  :  10.7717/peerj.4206

来源: DOAJ

【 摘 要 】

Targeting tyrosinase is considered to be an effective way to control the production of melanin. Tyrosinase inhibitor is anticipated to provide new therapy to prevent skin pigmentation, melanoma and neurodegenerative diseases. Herein, we report our results in identifying new tyrosinase inhibitors. The shape-based virtual screening was performed to discover new tyrosinase inhibitors. Thirteen potential hits derived from virtual screening were tested by biological determinations. Compound 5186-0429 exhibited the most potent inhibitory activity. It dose-dependently inhibited the activity of tyrosinase, with the IC50 values 6.2 ± 2.0 µM and 10.3 ± 5.4 µM on tyrosine and L-Dopa formation, respectively. The kinetic study of 5186-0429 demonstrated that this compound acted as a competitive inhibitor. We believe the discoveries here could serve as a good starting point for further design of potent tyrosinase inhibitor.

【 授权许可】

Unknown