Unexpected impact of esterification on the antioxidant activity and (photo)stability of a eumelanin from 5,6‐dihydroxyindole‐2‐carboxylic acid

Abstract

To inquire into the role of the carboxyl group as determinant of the properties of 5,6-dihydroxyindole melanins, melanins from aerial oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and its DHICA methyl ester (MeDHICA) were comparatively tested for their antioxidant activity. MALDI MS spectrometry analysis of MeDHICA melanin provided evidence for a collection of intact oligomers. EPR analysis showed g-values almost identical and signal amplitudes (ΔB) comparable to those of DHICA melanin, but spin density was one order of magnitude higher, with a different response to pH changes. Antioxidant assays were performed, and a model of lipid peroxidation was used to compare the protective effects of the melanins. In all cases, MeDHICA melanin performed better than DHICA melanin. This capacity was substantially maintained following exposure to air in aqueous buffer over 1 week or to solar simulator over 3 hr. Different from DHICA melanin, MeDHICA melanin was proved to be fairly soluble in different water-miscible organic solvents, suggesting its use in dermocosmetic applications.

Gelatin-Based Hydrogels for the Controlled Release of 5,6-Dihydroxyindole-2-Carboxylic Acid, a Melanin-Related Metabolite with Potent Antioxidant Activity

“…This result can be interpreted considering the higher release of the indoles in terms of rate and extent from HGel-C with respect to HGel-B. Previous studies on the antioxidant effect of the two indoles have shown an around 2.5-fold higher activity for DHICA with respect to MeDHICA in the DPPH assay [36]. This result allows to rationalize the effect on DPPH consumption observed for DHICA and MeDHICA incorporated into HGel-B (28 and 32%, respectively), in the light of the concentration of the indoles actually released in incubation medium after 6 h, that is 9  M and 19  M for DHICA and MeDHICA, respectively.…”

“…One of the advantages that should be offered by incorporation of melanin related indoles into a biopolymer like gelatin is the increase of the stability to aerial oxidation in aqueous neutral media of physiological relevance. This issue is more critical in the case of DHICA with respect to MeDHICA given its higher proness to oxidation as shown in our previous studies [36].…”

“…Phosphate buffer saline (PBS) 10× was purchased from VWR. DHICA and MeDHICA were prepared according to a procedure previously developed [36,37].…”

“…Within this framework in the present work, we have investigated the ability of gelatin-based hydrogels of incorporating and releasing under controlled conditions DHICA. The methyl ester of DHICA, MeDHICA, was also tested in view of its higher stability and different solubility profile [36]. Three different type of gelatin-based hydrogels were prepared as drug release systems: (a) pristine porcine skin type A gelatin (HGel-A); (b) pristine gelatin cross-linked by amide coupling of lysines and glutamic/aspartic acids (HGel-B), and (c) a gelatin/chitosan blend (HGel-C).…”

Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources

“…Alternatively, in the last years, other melanin-related compounds have been proposed to increase the absorption and general properties of natural melanin in order to be used in cosmeceutics. In this regard, in exploring the maintenance role of the carboxyl group in polymers, studies revealed that the use of DHICA methyl ester improves the antioxidant and protective effects of the final polymer, particularly by the higher absorption of UVA light [16,44].…”