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

Author:

Carradori Simone1ORCID,Angeli Andrea2ORCID,Sfragano Patrick S.3ORCID,Yzeiri Xheila345,Calamante Massimo34ORCID,Tanini Damiano3ORCID,Capperucci Antonella3,Kunstek Hannah67,Varbanov Mihayl78,Capasso Clemente9ORCID,Supuran Claudiu T.2ORCID

Affiliation:

1. Department of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

2. Neurofarba Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy

3. Department of Chemistry “Ugo Schiff”, University of Florence, Via Della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy

4. CNR-Institute of Chemistry of Organometallic Compounds (CNR-ICCOM), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy

5. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy

6. Institute of Molecular Biotechnology, Graz University of Technology, 8010 Graz, Austria

7. L2CM, Centre National de la Recherche Scientifique (CNRS), Université de Lorraine, 54000 Nancy, France

8. Laboratoire de Virologie, Centres Hospitaliers Régionaux Universitaires (CHRU) de Nancy Brabois, 54500 Vandœuvre-lès-Nancy, France

9. Department of Biology, Agriculture and Food Sciences, National Research Council (CNR), Institute of Biosciences and Bioresources, 80131 Naples, Italy

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.

Funder

Italian Ministry of University and Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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