2-S-Lipoylcaffeic Acid, a Natural Product-Based Entry to Tyrosinase Inhibition via Catechol Manipulation.

Raffaella Micillo,Alessandra Napolitano,Elio Pizzo,Marco D’Ischia,Valeria Pistorio,Lucia Panzella

doi:10.3390/biomimetics2030015

Raffaella Micillo, Alessandra Napolitano + Show 4 more

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https://doi.org/10.3390/biomimetics2030015

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Abstract

Conjugation of naturally occurring catecholic compounds with thiols is a versatile and facile entry to a broad range of bioinspired multifunctional compounds for diverse applications in biomedicine and materials science. We report herein the inhibition properties of the caffeic acid- dihydrolipoic acid S-conjugate, 2-S-lipoylcaffeic acid (LC), on mushroom tyrosinase. Half maximum inhibitory concentration (IC50) values of 3.22 ± 0.02 and 2.0 ± 0.1 µM were determined for the catecholase and cresolase activity of the enzyme, respectively, indicating a greater efficiency of LC compared to the parent caffeic acid and the standard inhibitor kojic acid. Analysis of the Lineweaver–Burk plot suggested a mixed-type inhibition mechanism. LC proved to be non-toxic on human keratinocytes (HaCaT) at concentrations up to 30 µM. These results would point to LC as a novel prototype of melanogenesis regulators for the treatment of pigmentary disorders.

Highlights

Several pigmentary disorders, such as melasma or lentigo, are associated with the overproduction or accumulation of melanin as the result of inflammatory responses or abnormal function of melanocytes inducing a local excess of pigmentation known as “hypermelanosis” [1,2,3]
Since skin complexion is under control of several factors, including activity, expression, and stability of tyrosinase and related enzymes, melanocytes homeostasis, and melanosome transfer to the keratinocytes, commercially available depigmenting agents and melanogenesis regulators usually act through different mechanisms [7,8]
The of synthesis of lipoylcaffeic acid (LC) of was carried a procedure previously reported for generation of the o‐quinone of caffeic acid by the regioselective hydroxylation of p‐coumaric acid with

Summary

Introduction

Several pigmentary disorders, such as melasma or lentigo, are associated with the overproduction or accumulation of melanin as the result of inflammatory responses or abnormal function of melanocytes inducing a local excess of pigmentation known as “hypermelanosis” [1,2,3]. Since skin complexion is under control of several factors, including activity, expression, and stability of tyrosinase and related enzymes, melanocytes homeostasis, and melanosome transfer to the keratinocytes, commercially available depigmenting agents and melanogenesis regulators usually act through different mechanisms [7,8]. One of the most common approaches for control of pigmentation involves the inhibition of tyrosinase (EC 1.14.18.1) [9,10], a copper-containing enzyme exhibiting cresolasic or monophenolasic activity (hydroxylation of monophenols to o-diphenols) and catecholasic or diphenolasic activity (dehydrogenation of catechols to o-quinones) by a mechanism involving electron exchange with the copper atoms. When considering a new tyrosinase inhibitor several factors should be taken into account, such as product efficacy, cytotoxicity, solubility, cutaneous absorption, and stability. Increasing attention has been paid to the adverse effects of depigmenting agents in vitro and in vivo, especially further

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