Resorcinol alkyl glucosides as potent tyrosinase inhibitors

Wakana Ishioka; Sayaka Oonuki; Takehiro Iwadate; Ken-Ichi Nihei

doi:10.1016/j.bmcl.2018.11.029

Resorcinol alkyl glucosides as potent tyrosinase inhibitors

Bioorg Med Chem Lett. 2019 Jan 15;29(2):313-316. doi: 10.1016/j.bmcl.2018.11.029. Epub 2018 Nov 14.

Authors

Wakana Ishioka¹, Sayaka Oonuki¹, Takehiro Iwadate², Ken-Ichi Nihei³

Affiliations

¹ Department of Applied Biological Chemistry, School of Agriculture, Utsunomiya University, Tochigi 321-0943, Japan.
² Department of Applied Life Science, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
³ Department of Applied Biological Chemistry, School of Agriculture, Utsunomiya University, Tochigi 321-0943, Japan; Department of Applied Life Science, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan. Electronic address: nihei98@cc.utsunomiya-u.ac.jp.

PMID: 30470492
DOI: 10.1016/j.bmcl.2018.11.029

Abstract

Resorcinol alkyl glucosides 7-12 were developed as novel tyrosinase inhibitors based on the structure of rhododendrin. These were synthesized from 2,4-dibenzyloxybenzaldehyde using either the Wittig or the Horner-Wadsworth-Emmons reaction with Koenigs-Knorr glycosylation as key steps. The tyrosinase inhibitory activity of 7-12 increased with the length of the alkyl spacer between resorcinol and glucose. The 50% inhibitory concentration (IC₅₀) of tetradecyl derivative 12 was 0.39 μM, making it the most potent of the compounds synthesized. The IC₅₀ of 8 (3.62 μM) with a propyl spacer was ca 10 times that of 7 (35.9 μM) with an ethyl spacer. This significant activity difference suggests that an interaction between resorcinol alkyl glucoside and tyrosinase may increase remarkably if the length of the alkyl spacer exceeds C₃.

Keywords: Alkyl spacer; Glycosylation; Resorcinol alkyl glucoside; Tyrosinase inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkylation
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Glucosides / chemical synthesis
Glucosides / chemistry
Glucosides / pharmacology*
Molecular Structure
Monophenol Monooxygenase / antagonists & inhibitors*
Monophenol Monooxygenase / metabolism
Resorcinols / chemical synthesis
Resorcinols / chemistry
Resorcinols / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Glucosides
Resorcinols
Monophenol Monooxygenase
resorcinol