Synthesis and Biological Activity Assessment of 2-Styrylbenzothiazoles as Potential Multifunctional Therapeutic Agents

• Published in: Antioxidants 2024-10, Vol.13 (10), p.1196
• Main Authors: Barbari, Riccardo, Bruggink, Vera, Hofstetter, Robert Klaus, Tupini, Chiara, Fagnani, Sofia, Baldini, Erika, Durini, Elisa, Lampronti, Ilaria, Vertuani, Silvia, Baldisserotto, Anna, Werz, Oliver, Manfredini, Stefano
• Format: Article
• Language: English
• Subjects: ant-inflammatory; Anti-inflammatory agents; Antioxidants; antitumor; Arachidonate 5-lipoxygenase; benzothiazole derivatives; Biological activity; Comparative analysis; Disease; Drug discovery; Identification and classification; Inflammation; Leukocytes (neutrophilic); Lipoxygenase; Melanoma; multifunctional; Mutation; Physiological aspects; Side effects; Skin cancer; Thiazoles; Ultraviolet radiation
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox13101196

A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours.