Structural Patterns Enhancing the Antibacterial Activity of Metallacarborane-Based Antibiotics.

Autor:	Cebula J; Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Fink K; Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Goldeman W; Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, 50-370 Wrocław, Poland., Szermer-Olearnik B; Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Nasulewicz-Goldeman A; Laboratory of Experimental Anticancer Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Psurski M; Laboratory of Experimental Anticancer Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Cuprych M; Laboratory of Experimental Anticancer Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Kędziora A; Department of Microbiology, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wrocław, Poland., Dudek B; Department of Microbiology, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wrocław, Poland., Bugla-Płoskońska G; Department of Microbiology, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wrocław, Poland., Chaszczewska-Markowska M; Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Gos M; Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Migdał P; Department of Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland., Goszczyński TM; Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2023 Nov 09; Vol. 66 (21), pp. 14948-14962. Date of Electronic Publication: 2023 Oct 30.
DOI:	10.1021/acs.jmedchem.3c01516
Abstrakt:	Healthcare systems heavily rely on antibiotics to treat bacterial infections, but the widespread presence of multidrug-resistant bacteria puts this strategy in danger. Novel drugs capable of overcoming current resistances are needed if our ability to treat bacterial infections is to be maintained. Boron clusters offer a valuable possibility to create a new class of antibiotics and expand the chemical space of antibiotics beyond conventional carbon-based molecules. In this work, we identified two promising structural patterns providing cobalta bis(dicarbollide)(COSAN)-based compounds with potent and selective activity toward Staphylococcus aureus (including clinical strains): introduction of the α-amino acid amide and addition of iodine directly to the metallacarborane cage. Furthermore, we found that proper hydrophilic-lipophilic balance is crucial for the selective activity of the tested compounds toward S. aureus over mammalian cells. The patterns proposed in this paper can be useful in the development of metallacarborane-based antibiotics with potent antibacterial properties and low cytotoxicity.
Databáze:	MEDLINE
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