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

• Main Authors: Riccardo Barbari (Author), Vera Bruggink (Author), Robert Klaus Hofstetter (Author), Chiara Tupini (Author), Sofia Fagnani (Author), Erika Baldini (Author), Elisa Durini (Author), Ilaria Lampronti (Author), Silvia Vertuani (Author), Anna Baldisserotto (Author), Oliver Werz (Author), Stefano Manfredini (Author)
• Format: Book
• Published: MDPI AG, 2024-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox13101196; 2076-3921
• Keywords: benzothiazole derivatives; multifunctional; antioxidants; antitumor; ant-inflammatory; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 13, Iss 10, p 1196 (2024)

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 <b>BZTst6</b> proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound <b>BZTst4</b> 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 IC₅₀ 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.