Photoactivatable Heptamethine-Based Carbonic Anhydrase Inhibitors Leading to New Anti-Antibacterial Agents

光激活的七甲碱基碳酸酐酶抑制剂可产生新的抗菌剂

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作者:Simone Carradori, Andrea Angeli, Patrick S Sfragano, Xheila Yzeiri, Massimo Calamante, Damiano Tanini, Antonella Capperucci, Hannah Kunstek, Mihayl Varbanov, Clemente Capasso, Claudiu T Supuran

Abstract

With the aim to propose innovative antimicrobial agents able to not only selectively inhibit bacterial carbonic anhydrases (CAs) but also to be photoactivated by specific wavelengths, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized by means of different spacers. The compounds displayed potent CA inhibition and a slight preference for bacterial isoforms. Furthermore, minimal inhibitory and bactericidal concentrations and the cytotoxicity of the compounds were assessed, thus highlighting a promising effect under irradiation against S. epidermidis. The hemolysis activity test showed that these derivatives were not cytotoxic to human red blood cells, further corroborating their favorable selectivity index. This approach led to the discovery of a valuable scaffold for further investigations.

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