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2-S-Lipoylcaffeic Acid, a Natural Product-Based Entry to Tyrosinase Inhibition via Catechol Manipulation
Raffaella Micillo1, Valeria Pistorio2, Elio Pizzo3
1Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. raffaella.micillo@unina.it.
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.
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