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

Qi Li; Hongyu Yang; Jun Mo; Yao Chen; Yue Wu; Chen Kang; Yuan Sun; Haopeng Sun

doi:10.7717/peerj.4206

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

PeerJ. 2018 Jan 26:6:e4206. doi: 10.7717/peerj.4206. eCollection 2018.

Authors

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

Affiliations

¹ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
² School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
³ Nanjing Duoyuan Biochemistry Co., Ltd., Nanjing, China.
⁴ Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America.
⁵ Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA, United States of America.

Abstract

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.

Keywords: Hit identification; Molecular shape; Tyrosinase inhibitor.

Grants and funding

This work was supported by grants 81402851 and 81573281 from the National Natural Science Foundation of China, and BK20140957 from the Natural Science Foundation of Jiangsu Province. Support was also recieved from Fundamental Research Funds for the Central Universities (2015ZD009), Jiangsu Qing Lan Project, Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP-PPZY2015A070) and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.