Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies

Sini Radhakrishnan; Ronald Shimmon; Costa Conn; Anthony Baker

doi:10.1016/j.bioorg.2015.10.003

Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies

Bioorg Chem. 2015 Dec:63:116-22. doi: 10.1016/j.bioorg.2015.10.003. Epub 2015 Oct 22.

Authors

Sini Radhakrishnan¹, Ronald Shimmon², Costa Conn², Anthony Baker²

Affiliations

¹ School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia. Electronic address: sinikaranayil@gmail.com.
² School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.

PMID: 26496408
DOI: 10.1016/j.bioorg.2015.10.003

Abstract

Polyphenol oxidase (Tyrosinase) has received great attention, since it is the key enzyme in melanin biosynthesis. In this study, novel hydroxy naphthylchalcone compounds were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 10.4μM and 14.4μM, respectively) than the positive control, kojic acid (IC50: 27.5μM). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their Ki values of 3.8μM and 4.5μM, respectively. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues. This study suggests hydroxy naphthylchalcone compounds to serve as promising candidates for use as depigmentation agents.

Keywords: Competitive; Docking; Reversible; Tyrosinase.

MeSH terms

Agaricales / enzymology
Catechol Oxidase / antagonists & inhibitors*
Catechol Oxidase / metabolism
Chalcones / chemical synthesis*
Chalcones / chemistry
Chalcones / pharmacology*
Dose-Response Relationship, Drug
Hydroxylation
Molecular Docking Simulation*
Molecular Structure
Naphthalenes / chemical synthesis*
Naphthalenes / chemistry
Naphthalenes / pharmacology*
Structure-Activity Relationship

Substances

Chalcones
Naphthalenes
Catechol Oxidase