Metal complexes as a promising source for new antibiotics
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...
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| Published in | Chemical science (Cambridge) Vol. 11; no. 1; pp. 2627 - 2639 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
14.03.2020
|
| Subjects | |
| Online Access | Get full text |
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| 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.
There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules. |
|---|---|
| AbstractList | There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules.
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. 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.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. 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 (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. 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. 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. 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. There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules. |
| Author | Zuegg, Johannes Elliott, Alysha G Rutledge, Peter J Dowson, Christopher Massi, Massimiliano Cooper, Matthew A Frei, Angelo Blaskovich, Mark A. T Baker, Murray King, A. Paden Willans, Charlotte E Todd, Matthew H Dujardin, Gilles Braese, Stefan Brown, Christopher Moat, John Chen, Feng Jung, Nicole Mansour, Ahmed M Mohamed, Heba A Renfrew, Anna K Sadler, Peter J Wilson, Justin J |
| AuthorAffiliation | The University of Sydney Centre for Superbug Solutions Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS) University College London University of Warwick Department of Chemistry and Chemical Biology School of Chemistry Department of Chemistry University of Leeds Chemistry Department School of Pharmacy School of Molecular and Life Sciences - Curtin Institute for Functional Materials and Interfaces University of Sydney Institute of Molecules and Matter of Le Mans (IMMM) Antimicrobial Screening Facility UMR 6283 CNRS The University of Western Australia Faculty of Science Cornell University Curtin University Karlsruhe Institute of Technology (KIT) The University of Queensland School of Medical Sciences (Discipline of Pharmacology) Institute of Organic Chemistry School of Molecular Sciences Institute for Molecular Bioscience School of Life Sciences Le Mans Université Cairo University |
| AuthorAffiliation_xml | – name: School of Medical Sciences (Discipline of Pharmacology) – name: Institute of Molecules and Matter of Le Mans (IMMM) – name: Department of Chemistry – name: Antimicrobial Screening Facility – name: School of Pharmacy – name: UMR 6283 CNRS – name: Centre for Superbug Solutions – name: The University of Western Australia – name: University of Warwick – name: The University of Queensland – name: Institute of Organic Chemistry – name: Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS) – name: Department of Chemistry and Chemical Biology – name: School of Molecular Sciences – name: University of Leeds – name: Cairo University – name: The University of Sydney – name: Karlsruhe Institute of Technology (KIT) – name: Institute for Molecular Bioscience – name: School of Life Sciences – name: Faculty of Science – name: Le Mans Université – name: Chemistry Department – name: Cornell University – name: Curtin University – name: University of Sydney – name: School of Molecular and Life Sciences - Curtin Institute for Functional Materials and Interfaces – name: School of Chemistry – name: University College London – name: g Antimicrobial Screening Facility , School of Life Sciences , University of Warwick , Gibbet Hill Road , Coventry CV4 7AL , UK – name: h Institute of Molecules and Matter of Le Mans (IMMM) , UMR 6283 CNRS , Le Mans Université , France – name: b School of Molecular Sciences , The University of Western Australia , Stirling Highway , 6009 Perth , Australia – name: l School of Chemistry , University of Leeds , Woodhouse Lane , Leeds LS2 9JT , UK – name: m School of Chemistry , The University of Sydney , Sydney , NSW 2006 , Australia – name: j Chemistry Department , Faculty of Science , Cairo University , Egypt – name: i Department of Chemistry and Chemical Biology , Cornell University , Ithaca , NY 14853 , USA – name: f Department of Chemistry , University of Warwick , Gibbet Hill Road , Coventry CV4 7AL , UK – name: k School of Molecular and Life Sciences – Curtin Institute for Functional Materials and Interfaces , Curtin University , Kent Street , 6102 Bentley WA , Australia – name: n School of Pharmacy , University College London , London , WC1N 1AX , UK – name: c Institute of Organic Chemistry , Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6 , 76131 Karlsruhe , Germany – name: e School of Medical Sciences (Discipline of Pharmacology) , University of Sydney , Australia – name: a Centre for Superbug Solutions , Institute for Molecular Bioscience , The University of Queensland , St. Lucia , Queensland 4072 , Australia . Email: angelo.frei.ch@gmail.com ; Email: m.blaskovich@uq.edu.au – name: d Institute of Biological and Chemical Systems – Functional Molecular Systems (IBCS-FMS) , Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz-Platz 1 , D-76344 Eggenstein-Leopoldshafen , Germany |
| Author_xml | – sequence: 1 givenname: Angelo surname: Frei fullname: Frei, Angelo – sequence: 2 givenname: Johannes surname: Zuegg fullname: Zuegg, Johannes – sequence: 3 givenname: Alysha G surname: Elliott fullname: Elliott, Alysha G – sequence: 4 givenname: Murray surname: Baker fullname: Baker, Murray – sequence: 5 givenname: Stefan surname: Braese fullname: Braese, Stefan – sequence: 6 givenname: Christopher surname: Brown fullname: Brown, Christopher – sequence: 7 givenname: Feng surname: Chen fullname: Chen, Feng – sequence: 8 givenname: Christopher surname: Dowson fullname: Dowson, Christopher – sequence: 9 givenname: Gilles surname: Dujardin fullname: Dujardin, Gilles – sequence: 10 givenname: Nicole surname: Jung fullname: Jung, Nicole – sequence: 11 givenname: A. Paden surname: King fullname: King, A. Paden – sequence: 12 givenname: Ahmed M surname: Mansour fullname: Mansour, Ahmed M – sequence: 13 givenname: Massimiliano surname: Massi fullname: Massi, Massimiliano – sequence: 14 givenname: John surname: Moat fullname: Moat, John – sequence: 15 givenname: Heba A surname: Mohamed fullname: Mohamed, Heba A – sequence: 16 givenname: Anna K surname: Renfrew fullname: Renfrew, Anna K – sequence: 17 givenname: Peter J surname: Rutledge fullname: Rutledge, Peter J – sequence: 18 givenname: Peter J surname: Sadler fullname: Sadler, Peter J – sequence: 19 givenname: Matthew H surname: Todd fullname: Todd, Matthew H – sequence: 20 givenname: Charlotte E surname: Willans fullname: Willans, Charlotte E – sequence: 21 givenname: Justin J surname: Wilson fullname: Wilson, Justin J – sequence: 22 givenname: Matthew A surname: Cooper fullname: Cooper, Matthew A – sequence: 23 givenname: Mark A. T surname: Blaskovich fullname: Blaskovich, Mark A. T |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32206266$$D View this record in MEDLINE/PubMed |
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| Snippet | There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug... There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against... |
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| SubjectTerms | Antibiotics Antimicrobial agents Chemistry Cobalt Coordination compounds Iridium Malaria Organic chemistry Platinum Silver Toxicity Zinc |
| Title | Metal complexes as a promising source for new antibiotics |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32206266 https://www.proquest.com/docview/2375920129 https://www.proquest.com/docview/2382660818 https://pubmed.ncbi.nlm.nih.gov/PMC7069370 |
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