Biological investigation of <i>N</i> -methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors
Ilaria D’Agostino, Githa Elizabeth Mathew, Paola Angelini, Roberto Venanzoni, Giancarlo Angeles Flores, Andrea Angeli, Simone Carradori, Beatrice Marinacci, Luigi Menghini, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Bijo Mathew, Claudiu T. Supuran
Abstract
The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1–9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.