Please login first
New heterocyclic polyphenols with skin anti-aging potential
* 1, 2 , 3, 4 , 5 , 6 , 7 , 7 , 8 , 9 , 10, 11 , 11 , 10, 11 , 9, 12 , * 13, 14
1  1 Laboratory of Organic and Pharmaceutical Chemistry (LQOF), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2  2 Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
3  Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal
4  CIIMAR – Centro Interdisciplinar de Investigação Marinha e Ambiental, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal
5  3Laboratório de Tecnologia Farmacêutica, Departamento do Medicamento, Faculdade de Farmácia, Universidade do Porto, Portugal
6  UCIBIO, REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal
7  UCIBIO/REQUIMTE, MedTec-Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Faculdade de Farmácia, Universidade do Porto, Portugal
8  University of Ferrara, Dept. of Life Sciences and Biotechnology, Via Fossato di Mortara 17/1944121 FERRARA, IItaly
9  Department of Chemical Sciences, Laboratory of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Porto, Portugal
10  7cE3c–Centre for Ecology, Evolution and Environmental Changes / Azorean Biodiversity Group 9501-801 Ponta Delgada, Portugal
11  8Faculdade de Ciências e Tecnologia, Universidade dos Açores 9501-801 Ponta Delgada, Portugal.
12  CIIMAR – Interdisciplinary Centre of Marine and Environmental Research, Portugal
13  a Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal
14  b Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Portugal

Published: 01 November 2019 by MDPI in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5
Abstract:

Xanthones or dibenzo-gamma-pyrones are heterocyclic polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. Structure-activity relationship studies emerged from a library of natural and synthetic polyoxygenated have suggested that xanthones with vicinal diol groups have promising antioxidant activity. Antioxidants have long been used in the cosmetic industry to prevent or minimize skin aging which is mediated by oxidative stress, making the search for new antioxidant agents highly desirable in this field.

Considering the structure-activity relationship studies, it was hypothesized that trioxygenated xanthones could be promising antioxidants with potential as skin anti-aging ingredients. Hence, the synthesis of trioxygenated xanthones was attempted by the Smiles rearrangement pathway and also via acyl radical cyclization. The Smiles rearrangement pathway failed to yield the ester intermediate that was essential in this approach and was therefore abandoned. In the acyl radical cyclization method it was possible to obtain the 1,4-dihydroxy-3-methoxy-9H-xanthen-9-one.

The antioxidant activity of this new xanthone as well as of four other polyoxygenated xanthones was evaluated by the DPPH assay, and two new derivatives showed IC50 values in the same range as the ascorbic acid. Almost all of the compounds were excellent tyrosinase inhibitors, more active than control inhibitor kojic acid. Concerning the other skin-degrading enzymes, the compounds tested were weak to moderate collagenase inhibitors, and showed no activity against elastase. The stability in presence of metal ions (FeCl3 and CuCl2) and dependence of the pH of their aqueous solutions was also studied, as well as their solubility in water and glycerol. Finally, the phototoxicity of the most promising xanthone was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested, which is an important requirement for topical ingredients.

Acknowledgements:

This work was developed under the Strategic Funding UID/Multi/04423/2019 and Project No. POCI-01-0145-FEDER-028736, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds, QREN,FEDER, COMPETE, by funding the cE3c centre (Ref. UID/BIA/00329/2019) and Azores DRCT for funding ABG. This work was also supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019.

Keywords: xanthones; antiaging; preclinical studies
Top