eprintid: 10094167 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/09/41/67 datestamp: 2020-03-30 09:52:08 lastmod: 2021-09-20 22:38:24 status_changed: 2020-03-30 09:52:08 type: article metadata_visibility: show creators_name: Frei, A creators_name: Zuegg, J creators_name: Elliott, AG creators_name: Baker, M creators_name: Braese, S creators_name: Brown, C creators_name: Chen, F creators_name: G Dowson, C creators_name: Dujardin, G creators_name: Jung, N creators_name: King, AP creators_name: Mansour, AM creators_name: Massi, M creators_name: Moat, J creators_name: Mohamed, HA creators_name: Renfrew, AK creators_name: Rutledge, PJ creators_name: Sadler, PJ creators_name: Todd, MH creators_name: Willans, CE creators_name: Wilson, JJ creators_name: Cooper, MA creators_name: Blaskovich, MAT title: Metal complexes as a promising source for new antibiotics ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G09 note: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (https://creativecommons.org/licenses/by/3.0/) abstract: 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. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance. date: 2020-03-14 date_type: published official_url: http://dx.doi.org/10.1039/c9sc06460e oa_status: green full_text_type: pub pmcid: PMC7069370 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1774128 doi: 10.1039/c9sc06460e pii: c9sc06460e lyricists_name: Todd, Matthew lyricists_id: MTODD88 actors_name: Wong, Ian actors_name: Harris, Jean actors_id: ICKWO00 actors_id: JAHAR68 actors_role: owner actors_role: impersonator full_text_status: public publication: Chemical Science volume: 11 number: 10 pagerange: 2627-2639 event_location: England citation: Frei, A; Zuegg, J; Elliott, AG; Baker, M; Braese, S; Brown, C; Chen, F; ... Blaskovich, MAT; + view all <#> Frei, A; Zuegg, J; Elliott, AG; Baker, M; Braese, S; Brown, C; Chen, F; G Dowson, C; Dujardin, G; Jung, N; King, AP; Mansour, AM; Massi, M; Moat, J; Mohamed, HA; Renfrew, AK; Rutledge, PJ; Sadler, PJ; Todd, MH; Willans, CE; Wilson, JJ; Cooper, MA; Blaskovich, MAT; - view fewer <#> (2020) Metal complexes as a promising source for new antibiotics. Chemical Science , 11 (10) pp. 2627-2639. 10.1039/c9sc06460e <https://doi.org/10.1039/c9sc06460e>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10094167/1/c9sc06460e.pdf