Work

In the search for new gold metalloantibiotics: In vitro evaluation of Au(III) (C^S)-cyclometallated complexes

Year: 2024

Type: article

Abstract: A series of (C^S)-cyclometallated Au(III) cationic complexes of general formula [Au(dppta)(dtc)] + , [Au(dppta)(azmtd)] + and [Au(dppta)(azc)Cl] + (dppta = N,N-diisopropyl- P , P -diphenylphosphinothioic amide-κ 2 C,S; dtc = dithiocarbamate-κ 2 S,S′; azc = azolium-2-dithiocarboxylate-κ 1 S; azmdt = azol( in )ium-2-(methoxy)methanedithiol-κ 2 S,S′) were synthetized and tested against a panel of bacterial strains belonging to different Gram-positive and Gram-negative species of the ESKAPE group of pathogens. Among the tested compounds, complex 4c had the higher Therapeutic Index (TI) against multidrug resistant strains of S. aureus , S. epidermidis and A. baumannii , showing a more favourable cytotoxicity profile than the reference gold metalloantibiotic Auranofin. © 2024 xxxxxxxx. Hosting by Elsevier B.V. All rights reserved. In this work, we report a series of (C^S)-cyclometallated gold(III) cationic complexes with potent antibacterial activity against different species of clinically relevant Gram-positive and Gram-negative pathogenic bacteria. Importantly, a complex exhibiting low cytotoxicity towards mammalian cells was found, indicating high selectivity. • Cyclometallated gold(III) cationic complexes display potent antibacterial activity. • Gold(III) cationic complexes show selectivity for Gram-positive strains. • However, they also display remarkable activity against Gram-negative A. baumannii . • The ligands are suitable to stabilize gold(III) under physiological conditions. • A complex exhibiting low cytotoxicity towards mammalian cells was found.

Source: Journal of Inorganic Biochemistry

DOI: 10.1016/j.jinorgbio.2024.112735

Authors: Paula Pérez-Ramos, Yaiza Gabasa, Enmanuel Cornielle, Humberto Rodríguez-Solla, Sara M. Soto, Raquel G. Soengas