Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

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.

Graphical Abstract

Keywords:

• Thiosemicarbazones
• antimicrobial agents
• Escherichia coli
• dermatophytes
• carbonic anhydrases

Acknowledgements

The authors deeply acknowledge the Researchers Supporting Program (TUMA-Project-2021-6), AlMaarefa University, Riyadh, Saudi Arabia for supporting steps of this work.

Author contributions

S.C., C.T.S. – conceptualisation; B.M., G.E.M., M.A.A., M.M.G. – synthesis of the compounds; S.C., B.Mar. – design of the experiments; I.D.A., S.C., L.M. – data analysis; P.A., R.V., and G.A.F.; biological evaluation; C.T.S. and A.A. – enzymatic assays; S.C., C.T.S. – supervision; I.D.A., B.Mar., S.C. – writing, original draft preparation. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. No potential conflict of interest was reported by all authors. CT Supuran is Editor-in-Chief of the Journal of Enzyme Inhibition and Medicinal Chemistry. He was not involved in the assessment, peer review, or decision-making process of this paper. The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by a grant from the Italian Ministry of University and Research under the FISR program, project FISR_04819 BacCAD to C.T.S. and S.C.