Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands

Bence Balázs; Zoltán Tóth; István Kacsir; Adrienn Sipos; Péter Buglyó; László Somsák; Éva Bokor; Gábor Kardos; Péter Bai

doi:10.3389/fchem.2022.868234

Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands

Front Chem. 2022 Apr 12:10:868234. doi: 10.3389/fchem.2022.868234. eCollection 2022.

Authors

Bence Balázs¹, Zoltán Tóth¹, István Kacsir^{2

3}, Adrienn Sipos⁴, Péter Buglyó⁵, László Somsák², Éva Bokor², Gábor Kardos¹, Péter Bai^{4

6

7}

Affiliations

¹ Department of Metagenomics, University of Debrecen, Debrecen, Hungary.
² Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary.
³ Doctoral School of Chemistry, University of Debrecen, Debrecen, Hungary.
⁴ Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁵ Department of Inorganic and Analytical Chemistry, Faculty of Sciences and Technology, University of Debrecen, Debrecen, Hungary.
⁶ NKFIH-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary.
⁷ Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Abstract

Bacterial resistance to antibiotics is an ever-growing problem in heathcare. We have previously identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type complexes with bidentate monosaccharide ligands possessing cytostatic properties against carcinoma, lymphoma and sarcoma cells with low micromolar or submicromolar IC₅₀ values. Importantly, these complexes were not active on primary, non-transformed cells. These complexes have now been assessed as to their antimicrobial properties and found to be potent inhibitors of the growth of reference strains of Staphylococcus aureus and Enterococcus faecalis (Gram-positive species), though the compounds proved inactive on reference strains of Pseudomonas aerugonisa, Escherichia coli, Candida albicans, Candida auris and Acinetobacter baumannii (Gram-negative species and fungi). Furthermore, clinical isolates of Staphylococcus aureus and Enterococcus sp. (both multiresistant and susceptible strains) were also susceptible to the organometallic complexes in this study with similar MIC values as the reference strains. Taken together, we identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type antineoplastic organometallic complexes which also have antimicrobial activity among Gram-positive bacteria. These compounds represent a novel class of antimicrobial agents that are not detoxified by multiresistant bacteria suggesting a potential to be used to combat multiresistant infections.

Keywords: MRSA; VRE; glycosyl heterocycle; gram positive; half-sandwich; oxadiazole; platinum-group metal complexes; triazole.