Dataset Information

2-Hydroxypyridine-N-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors.

ABSTRACT: With the aim to develop effective and selective human tyrosinase inhibitors, we investigated aurone derivatives whose B-ring was replaced by a non-oxidizable 2-hydroxypyridine-N-oxide (HOPNO) moiety. These aurones were synthesized and evaluated as inhibitors of purified human tyrosinase. Excellent inhibition activity was revealed and rationalized by theoretical calculations. The aurone backbone was especially found to play a crucial role, as the HOPNO moiety alone provided very modest activity on human tyrosinase. Furthermore, the in vitro activity was confirmed by measuring the melanogenesis suppression ability of the compounds in melanoma cell lysates and whole cells. Our study reveals that HOPNO-embedded 6-hydroxyaurone is to date the most effective inhibitor of isolated human tyrosinase. Owing to its low toxicity and its high inhibition activity, it could represent a milestone on the path toward new valuable agents in dermocosmetics, as well as in medical fields where it was recently suggested that tyrosinase could play key roles.

SUBMITTER: Haudecoeur R

PROVIDER: S-EPMC5238473 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

2-Hydroxypyridine-<i>N</i>-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors.

Haudecoeur Romain R Carotti Marcello M Gouron Aurélie A Maresca Marc M Buitrago Elina E Hardré Renaud R Bergantino Elisabetta E Jamet Hélène H Belle Catherine C Réglier Marius M Bubacco Luigi L Boumendjel Ahcène A

ACS medicinal chemistry letters 20161117 1

With the aim to develop effective and selective human tyrosinase inhibitors, we investigated aurone derivatives whose B-ring was replaced by a non-oxidizable 2-hydroxypyridine-<i>N</i>-oxide (HOPNO) moiety. These aurones were synthesized and evaluated as inhibitors of purified human tyrosinase. Excellent inhibition activity was revealed and rationalized by theoretical calculations. The aurone backbone was especially found to play a crucial role, as the HOPNO moiety alone provided very modest act ...[more]

PMID: 28105275

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Project description:Background and purposeTyrosinase enzyme has a key role in melanin biosynthesis by converting tyrosine into dopaquinone. It also participates in the enzymatic browning of vegetables by polyphenol oxidation. Therefore, tyrosinase inhibitors are useful in the fields of medicine, cosmetics, and agriculture. Many tyrosinase inhibitors having drawbacks have been reported to date; so, finding new inhibitors is a great need.Experimental approachA variety of 6-hydroxy-3,4-dihydronaphthalenone chalcone-like analogs (C1-C10) have been synthesized by aldol condensation of 6-hydroxy tetralone and differently substituted benzaldehydes. The compounds were evaluated for their inhibitory effect on mushroom tyrosinase by a spectrophotometric method. Moreover, the inhibition manner of the most active compound was determined by Lineweaver-Burk plots. Docking study was done using AutoDock 4.2. The drug-likeness scores and ADME features of the active derivatives were also predicted.Results/findingsMost of the compounds showed remarkable inhibitory activity against the tyrosinase enzyme. 6-Hydroxy-2-(3,4,5-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one (C2) was the most potent derivative amongst the series with an IC50 value of 8.8 μM which was slightly more favorable to that of the reference kojic acid (IC50 = 9.7 μM). Inhibitory kinetic studies revealed that C2 behaves as a competitive inhibitor. According to the docking results, compound C2 formed the most stable enzyme-inhibitor complex, mainly via establishing interactions with the two copper ions in the active site. In silico drug-likeness and pharmacokinetics predictions for the proposed tyrosinase inhibitors revealed that most of the compounds including C2 have proper drug-likeness scores and pharmacokinetic properties.Conclusion and implicationsTherefore, C2 could be suggested as a promising tyrosinase inhibitor that might be a good lead compound in medicine, cosmetics, and the food industry, and further drug development of this compound might be of great interest.

Dataset Information

2-Hydroxypyridine-N-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors.

Publications

2-Hydroxypyridine-<i>N</i>-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors.

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