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Metal complexes as a promising source for new antibiotics

Frei, Angelo; Zuegg, Johannes; Elliott, Alysha G.; Baker, Murray; Braese, Stefan; Brown, Christopher; Chen, Feng; Dowson, Christopher G.; Dujardin, Gilles; Jung, Nicole; King, A. Paden; Mansour, Ahmed M.; Massi, Massimiliano; Moat, John; Mohamed, Heba A.; Renfrew, Anna K.; Rutledge, Peter J.; Sadler, Peter J.; Todd, Matthew H.; Willans, Charlotte E.; ... mehr

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000118067
Veröffentlicht am 03.04.2020
DOI: 10.1039/c9sc06460e
Zitationen: 34
Web of Science
Zitationen: 27
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2041-6520, 2041-6539
KITopen-ID: 1000118067
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Chemical science
Verlag Royal Society of Chemistry (RSC)
Band 11
Heft 10
Seiten 2627–2639
Nachgewiesen in Web of Science
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