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Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation

Xue, Songtao; Li, Zhiwei; Ze, Xiaotong; Wu, Xiuyuan; He, Chen; Shuai, Wen; Marlow, Maria; Chen, Jian; Scurr, David; Zhu, Zheying; Xu, Jinyi; Xu, Shengtao

Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation Thumbnail


Authors

Songtao Xue

Zhiwei Li

Xiaotong Ze

Xiuyuan Wu

Chen He

Wen Shuai

JIAN CHEN JIAN.CHEN@NOTTINGHAM.AC.UK
Associate Professor

DAVID SCURR DAVID.SCURR@NOTTINGHAM.AC.UK
Principal Research Fellow

ZHEYING ZHU Zheying.Zhu@nottingham.ac.uk
Associate Professor in International Pharmacy and Traditional Medicines

Jinyi Xu

Shengtao Xu



Abstract

Excessive melanin deposition may lead to a series of skin disorders. The production of melanin is carried out by melanocytes, in which the enzyme tyrosinase performs a key role. In this work, we identified a series of novel tyrosinase inhibitor hybrids with a dihydrochalcone skeleton and resorcinol structure, which can inhibit tyrosinase activity and reduce the melanin content in the skin. Compound 11c possessed the most potent activity against tyrosinase, showing IC50 values at nanomolar concentration ranges, along with significant antioxidant activity and low cytotoxicity. Furthermore, in vitro permeation tests, supported by HPLC analysis and 3D OrbiSIMS imaging visualization, revealed the excellent permeation of 11c. More importantly, compound 11c reduced the melanin content on UV-induced skin pigmentation in a guinea pig model in vivo. These results suggest that compound 11c may serve as a promising potent tyrosinase inhibitor for the development of a potential therapy to treat skin hyperpigmentation.

Citation

Xue, S., Li, Z., Ze, X., Wu, X., He, C., Shuai, W., …Xu, S. (2023). Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation. Journal of Medicinal Chemistry, 66(7), 5099–5117. https://doi.org/10.1021/acs.jmedchem.3c00012

Journal Article Type Article
Acceptance Date Mar 9, 2023
Online Publication Date Mar 20, 2023
Publication Date Mar 20, 2023
Deposit Date Mar 21, 2023
Publicly Available Date Mar 21, 2024
Journal Journal of Medicinal Chemistry
Print ISSN 0022-2623
Electronic ISSN 1520-4804
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 66
Issue 7
Pages 5099–5117
DOI https://doi.org/10.1021/acs.jmedchem.3c00012
Keywords Anatomy, Inhibition, Inhibitors, Ions, Peptides and proteins
Public URL https://nottingham-repository.worktribe.com/output/18808553
Publisher URL https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00012
Additional Information This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Journal of Medicinal Chemistry after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00012.

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