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

Victoria C. Nolan; Laia Rafols; James Harrison; Joan J. Soldevila-Barreda; Marialuisa Crosatti; Natalie J. Garton; Malgorzata Wegrzyn; Danielle L. Timms; Colin C. Seaton; Helen Sendron; Maria Azmanova; Nicolas P.E. Barry; Anaïs Pitto-Barry; Jonathan A.G. Cox

doi:10.1016/j.crmicr.2021.100099

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

Victoria C. Nolan, Laia Rafols, James Harrison, Joan J. Soldevila-Barreda, Marialuisa Crosatti, Natalie J. Garton, Malgorzata Wegrzyn, Danielle L. Timms, Colin C. Seaton, Helen Sendron, Maria Azmanova, Nicolas P.E. Barry, Anaïs Pitto-Barry, Jonathan A.G. Cox^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	100099
Journal	Current Research in Microbial Sciences
Volume	3
Early online date	16 Dec 2021
DOIs	https://doi.org/10.1016/j.crmicr.2021.100099
Publication status	Published - Jan 2022

Bibliographical note

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.

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Indole-containing arene-ruthenium complexes
Creative Commons Attribution 4.0 International (CC BY 4.0)
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Cite this

Nolan, V. C., Rafols, L., Harrison, J., Soldevila-Barreda, J. J., Crosatti, M., Garton, N. J., Wegrzyn, M., Timms, D. L., Seaton, C. C., Sendron, H., Azmanova, M., Barry, N. P. E., Pitto-Barry, A., & Cox, J. A. G. (2022). Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria. Current Research in Microbial Sciences, 3, Article 100099. https://doi.org/10.1016/j.crmicr.2021.100099

@article{08051ad793d343a29ab2e10e13dd69ac,

title = "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.",

author = "Nolan, {Victoria C.} and Laia Rafols and James Harrison and Soldevila-Barreda, {Joan J.} and Marialuisa Crosatti and Garton, {Natalie J.} and Malgorzata Wegrzyn and Timms, {Danielle L.} and Seaton, {Colin C.} and Helen Sendron and Maria Azmanova and Barry, {Nicolas P.E.} and Ana{\"i}s Pitto-Barry and Cox, {Jonathan A.G.}",

note = "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.",

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Nolan, VC, Rafols, L, Harrison, J, Soldevila-Barreda, JJ, Crosatti, M, Garton, NJ, Wegrzyn, M, Timms, DL, Seaton, CC, Sendron, H, Azmanova, M, Barry, NPE, Pitto-Barry, A & Cox, JAG 2022, 'Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria', Current Research in Microbial Sciences, vol. 3, 100099. https://doi.org/10.1016/j.crmicr.2021.100099

TY - JOUR

T1 - Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria

AU - Nolan, Victoria C.

AU - Rafols, Laia

AU - Harrison, James

AU - Soldevila-Barreda, Joan J.

AU - Crosatti, Marialuisa

AU - Garton, Natalie J.

AU - Wegrzyn, Malgorzata

AU - Timms, Danielle L.

AU - Seaton, Colin C.

AU - Sendron, Helen

AU - Azmanova, Maria

AU - Barry, Nicolas P.E.

AU - Pitto-Barry, Anaïs

AU - Cox, Jonathan A.G.

N1 - 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.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

UR - https://www.sciencedirect.com/science/article/pii/S2666517421000791?via%3Dihub#ack0001

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U2 - 10.1016/j.crmicr.2021.100099

DO - 10.1016/j.crmicr.2021.100099

M3 - Article

SN - 2666-5174

VL - 3

JO - Current Research in Microbial Sciences

JF - Current Research in Microbial Sciences

M1 - 100099

ER -

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

Abstract

Bibliographical note

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Investigating Novel Antimicrobial Strategies to Target Mycobacterium abscessus Infections

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

Abstract

Bibliographical note

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Student theses

Investigating Novel Antimicrobial Strategies to Target Mycobacterium abscessus Infections

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