In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives
Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17-19, I-44121 Ferrara, Italy
Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, University Campus, S.P. n° 8, Km 0.700, I-09042 Monserrato (CA), Italy
Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara 74, I-44121 Ferrara, Italy
Department of Life Sciences and Biotechnology, Section of Pharmaceutical Biology, University of Ferrara, Piazzale Luciano Chiappini 3, I-44123 Malborghetto di Boara (FE), Italy
Author to whom correspondence should be addressed.
These authors equally contribute to the present paper.
Pharmaceuticals 2020, 13(4), 68; https://doi.org/10.3390/ph13040068
Received: 24 February 2020 / Revised: 10 April 2020 / Accepted: 14 April 2020 / Published: 15 April 2020
(This article belongs to the Section Medicinal Chemistry)
In the search of multifunctional compounds we designed benzimidazole derivatives endowed with phenolic hydroxy groups and a hydrazone moiety as potential radical-scavenger and the antioxidant agents. The target molecules have been prepared by a simple synthetic procedure and tested for their antioxidant activity by DPPH, FRAP, and ORAC test, for photoprotective activity against UV rays and for antiproliferative activity against Colo-38 melanoma cells. Furthermore, two different dermocosmetic formulations were prepared with the compounds endowed with the best antioxidant and photoprotective profile and their release from formulation evaluated using Franz Cells system. High antioxidant activity is related to the presence of at least two hydroxy groups on arylidene moiety of benzimidazoles. Structure activity analysis revealed that the position of hydroxy groups is crucial for antioxidant activity as well as the presence of a 2-hydroxy-4-(diethylamino)arylidene group. The same correlation pattern was found to be related to photoprotective activity resulting in an UVA Protection Factor better than the commercial solar filter PBSA and antiproliferative activity against melanoma cells without producing cytotoxicity on normal keratinocytes. The release analysis indicated that high antioxidant activities are achieved with limited release at concentration compatible with the use as UV sunscreen filter.