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Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection.
Sovari, Sara Nasiri; Radakovic, Natasa; Roch, Paul; Crochet, Aurélien; Pavic, Aleksandar; Zobi, Fabio.
Afiliação
  • Sovari SN; Department of Chemistry, Fribourg University, Chemin Du Musée 9, 1700, Fribourg, Switzerland.
  • Radakovic N; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042, Belgrade, Serbia.
  • Roch P; Department of Chemistry, Fribourg University, Chemin Du Musée 9, 1700, Fribourg, Switzerland.
  • Crochet A; Department of Chemistry, Fribourg University, Chemin Du Musée 9, 1700, Fribourg, Switzerland.
  • Pavic A; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042, Belgrade, Serbia. Electronic address: sasapavic@imgge.bg.ac.rs.
  • Zobi F; Department of Chemistry, Fribourg University, Chemin Du Musée 9, 1700, Fribourg, Switzerland. Electronic address: fabio.zobi@unifr.ch.
Eur J Med Chem ; 226: 113858, 2021 Dec 15.
Article em En | MEDLINE | ID: mdl-34562853
Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC doses as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Candida albicans / Candidíase / Staphylococcus aureus Resistente à Meticilina / Antibacterianos / Antifúngicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Candida albicans / Candidíase / Staphylococcus aureus Resistente à Meticilina / Antibacterianos / Antifúngicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article