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

PeerJ

article

Qi Li¹  Hongyu Yang¹  Jun Mo¹  Yao Chen²  Yue Wu³  Chen Kang⁴  Yuan Sun⁵  Haopeng Sun¹ 

[1] Department of Medicinal Chemistry, China Pharmaceutical University;School of Pharmacy, Nanjing University of Chinese Medicine;Nanjing Duoyuan Biochemistry Co., Ltd.;Department of Internal Medicine, Carver College of Medicine, University of Iowa;Department of Biochemistry and Molecular Medicine, University of California

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

DOI  :  10.7717/peerj.4206

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 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】

CC BY