Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria

Abstract

Antimicrobial resistant (AMR) bacteria are emerging and spreading globally, threatening our ability to treat common infectious diseases. The development of new classes of antibiotics able to kill or inhibit the growth of such AMR bacteria through novel mechanisms of action is therefore urgently needed. Here, a new family of indole-containing arene ruthenium organometallic compounds are screened against several bacterial species and drug resistant strains. The most active complex [(p-cym)Ru(O-cyclohexyl-1H-indole-2-carbothioate)Cl] (3) shows growth inhibition and bactericidal activity against different organisms (Acinetobacter baumannii, Mycobacterium abscessus, Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica serovar typhi and Escherichia coli), demonstrating broad-spectrum inhibitory activity. Importantly, this compound series exhibits low toxicity against human cells. Owing to the novelty of the antibiotic family, their moderate cytotoxicity, and their inhibitory activity against Gram positive, Gram negative and acid-fast, antibiotic resistant microorganisms, this series shows significant promise for further development.

Publication DOI: https://doi.org/10.1016/j.crmicr.2021.100099
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: Creative Commons Attribution 4.0 International (CC BY 4.0) Funding: .P.E.B. acknowledges the support of the Royal Society (University Research Fellowship No. UF150295 to N.P.E.B.), the University of Bradford, and by the Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation Springboard Award [SBF003\1170 to N.P.E.B.]. J.A.G.C. is grateful to the Academy of Medical Sciences, Global Challenges Research Fund, Birmingham Women's and Children's Hospital Charity Research Foundation and Give A Child Health Fund for their continued support of the Mycobacterial Research Group at Aston University. This research was funded by the Academy of Medical Sciences/the British Heart Foundation/the Government Department of Business, Energy and Industrial Strategy/Global Challenges Research Fund/the Wellcome Trust Springboard Award [SBF003\1088]. VCN is supported with a PhD Studentship jointly funded by Give A Child Health Fund and Aston University.
Uncontrolled Keywords: Microbiology,Immunology and Microbiology (miscellaneous) ,Infectious Diseases,Microbiology (medical)
Publication ISSN: 2666-5174
Last Modified: 12 Jun 2024 07:24
Date Deposited: 04 Jan 2022 13:34
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Related URLs: https://www.sci ... %3Dihub#ack0001 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-01
Published Online Date: 2021-12-16
Accepted Date: 2021-12-01
Authors: Nolan, Victoria C.
Rafols, Laia
Harrison, James
Soldevila-Barreda, Joan J.
Crosatti, Marialuisa
Garton, Natalie J.
Wegrzyn, Malgorzata
Timms, Danielle L.
Seaton, Colin C.
Sendron, Helen
Azmanova, Maria
Barry, Nicolas P.E.
Pitto-Barry, Anaïs
Cox, Jonathan A.G. (ORCID Profile 0000-0001-5208-4056)

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