Boosting Antibiotic Efficacy of Azole Drugs against Methicillin‐Resistant <i>Staphylococcus Aureus</i> by Coordination to Rhenium Carbonyl Complexes

Schindler, Kevin; Demirci, Gozde; Tran, Bettina; Sovari, Sara Nasiri; Cortat, Youri; De Sousa, Nicolas F. Rosa; Velti, Carola; Chapuis, Baptiste; Crochet, Aurélien; Pavic, Aleksandar; Djuris, Jelena; Salentinig, Stefan; Zobi, Fabio

doi:10.1002/cbic.202500368

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chembiochem-2025-schindler-boostingantibioticefficacyofazoledrugsagainstmethicillinresistantstaphylococcus

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Boosting Antibiotic Efficacy of Azole Drugs against Methicillin‐Resistant Staphylococcus Aureus by Coordination to Rhenium Carbonyl Complexes

DOKPE

Schindler, Kevin ORCID University of Fribourg
Demirci, Gozde ORCID University of Fribourg
Tran, Bettina University of Fribourg
Sovari, Sara Nasiri University of Fribourg
Cortat, Youri ORCID University of Fribourg
De Sousa, Nicolas F. Rosa University of Fribourg
Velti, Carola University of Fribourg
Chapuis, Baptiste University of Fribourg
Crochet, Aurélien ORCID University of Fribourg
Pavic, Aleksandar ORCID University of Belgrade, Serbia
Djuris, Jelena ORCID University of Belgrade, Serbia
Salentinig, Stefan University of Fribourg
Zobi, Fabio ORCID University of Fribourg

2025

Published in:

ChemBioChem. - Chichester, UK: Wiley. - 2025

English In this study, a library of rhenium di- and tricarbonyl complexes featuring various antimicrobial azoles as monodentate ligands was synthesized and characterized. Their antimicrobial activity was evaluated against both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, and selected compounds were also assessed for cytotoxicity, yielding promising therapeutic indices. Notably, the complexation of antifungal azoles to the rhenium core enhanced antimicrobial efficacy, with a compound exhibiting up to a 32-fold improvement in MIC values relative to the parent azole. Structure-activity relationships indicated that cationic fac-[Re(CO)₃]⁺ complexes consistently outperformed their cis-[Re(CO)₂]⁺ counterparts, and mechanistic studies suggest that active complexes disrupt bacterial membrane integrity and interfere with the electron transport chain. Complementary small-angle X-ray scattering and in silico analysis corroborate these findings, offering insights into the mechanism of action of this family of complexes.

Faculty

Faculté des sciences et de médecine

Department

Département de Chimie

Language