Correction: Metal complexes as a promising source for new antibiotics

Frei, Angelo; Zuegg, Johannes; Elliott, Alysha G.; Baker, Murray V.; Braese, Stefan; Brown, Christopher; Chen, Feng; Dowson, Christopher G.; Dujardin, Gilles; Jung, Nicole; King, Anna; 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.; Wilson, Justin J.; Cooper, Matthew A.; Blaskovich, Mark A. T.

doi:10.1039/d0sc90075c

Cited by 7 publications

(7 citation statements)

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“…In the past decade, many luminescent metal complexes with exceedingly good photophysical and photochemical properties have been widely recognized as photosensitizers, − which were applied in photodynamic therapy (PDT) and photoactivated chemotherapy of tumor. − In addition to the research on tumor, metal complexes as promising antibiotics have become an effective means to combat various bacterial infections as well, especially for infections caused by MDR bacteria. − For example, a photoactive ruthenium(II) complex modified with isoniazid against tuberculosis was reported by Peter et al The isoniazid can be released from the Ru(II) complex under 465 nm blue light irradiation, and the Ru(II) complex showed more efficiency toward mycobacteria compared with isoniazid when photoactivated . They further synthesized a series of organoiridium(III) complexes containing a chelated biguanide ligand.…”

Section: Introductionmentioning

confidence: 99%

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy

Luo

Wang

et al. 2023

J. Med. Chem.

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Photoactive antibacterial therapy is one of the novel therapeutic methods that has great application potential and prospects for curbing bacterial infections. In this work, a photoactivated iridium complex (Ir–Cl) is synthesized for photoactive antibacterial research. Ir–Cl exhibits photoacidolysis, which can generate H+ and be converted into a photolysis product Ir–OH under blue light irradiation. At the meantime, this process is accompanied by 1O2 generation. Notably, Ir–Cl can selectively permeate S. aureus and exhibit excellent photoactive antibacterial activity. Mechanism studies show that Ir–Cl can ablate bacterial membranes and biofilms under light irradiation. Metabolomics analysis proves that Ir–Cl with light exposure mainly disturbs some amino acids’ degradation (e.g., valine, leucine, isoleucine, arginine) and pyrimidine metabolism, which indirectly causes the ablation of biofilms and ultimately produces irreversible damage to S. aureus. This work provides guidance for metal complexes in antibacterial application.

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Section: Introductionmentioning

confidence: 99%

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy

Luo

Wang

et al. 2023

J. Med. Chem.

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“…Metal complexes reached clinical trials for the treatment of various diseases and some compounds show also interesting antibacterial activity ( 10 – 12 ). However, the use of metal-based compounds as antibiotics is not widespread, and only a limited number of compounds have undergone clinical trials ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro antibacterial activity of dinuclear thiolato-bridged ruthenium(II)-arene compounds

Bugnon,

Melendez,

Desiatkina

et al. 2023

Microbiol Spectr

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The antibacterial activity of 22 thiolato-bridged dinuclear ruthenium(II)-arene compounds was assessed in vitro against Escherichia coli , Streptococcus pneumoniae , and Staphylococcus aureus . None of the compounds efficiently inhibited the growth of the three E. coli strains tested, and only compound 5 exhibited a medium activity against this bacterium [MIC (minimum inhibitory concentration) of 25 µM]. However, a significant antibacterial activity was observed against S. pneumoniae , with MIC values ranging from 1.3 to 2.6 µM for compounds 1–3 , 5, and 6 . Similarly, compounds 2 , 5–7, and 20–22 had MIC values ranging from 2.5 to 5 µM against S. aureus . The tested diruthenium compounds have a bactericidal effect significantly faster than that of penicillin. Fluorescence microscopy assays performed on S. aureus using the BODIPY-tagged diruthenium complex 15 showed that this type of metal compound enters the bacteria and does not accumulate in the cell wall of gram-positive bacteria. Cellular internalization was further confirmed by inductively coupled plasma mass spectrometry experiments. The nature of the substituents anchored on the bridging thiols and the compounds molecular weight appears to significantly influence the antibacterial activity. Thus, if overall a decrease of the bactericidal effect with the increase of compounds’ molecular weight is observed, however, the complexes bearing larger benzo-fused lactam substituents had low MIC values. This first antibacterial activity screening demonstrated that the thiolato-diruthenium compounds exhibit promising activity against S. aureus and S. pneumoniae and deserve to be considered for further studies. IMPORTANCE The in vitro assessment of diruthenium(II)-arene compounds against Escherichia coli , Streptococcus pneumoniae , and Staphylococcus aureus showed a significant antibacterial activity of some compounds against S. pneumoniae , with minimum inhibitory concentration (MIC) values ranging from 1.3 to 2.6 µM, and a medium activity against E. coli , with MIC of 25 µM. The nature of the substituents anchored on the bridging thiols and the compounds molecular weight appear to significantly influence the antibacterial activity. Fluorescence microscopy showed that these ruthenium compounds enter the bacteria and do not accumulate in the cell wall of gram-positive bacteria. These diruthenium(II)-arene compounds exhibit promising activity against S. aureus and S. pneumoniae and deserve to be considered for further studies, especially the compounds bearing larger benzo-fused lactam substituents.

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“…Another promising, yet largely untapped, resource toward the development of new antibacterial agents is the use of metal complexes. , Coordination compounds offer unique mechanisms of action, charges, and a broad range of geometries, which may be beneficial in addressing currently known bacterial resistance mechanisms . Numerous examples show antimicrobial activity of transition metal coordination complexes and bio-organometallic derivatives that are typically higher for the metal-containing coordination compound than for the free ligands. − However, many complexes show limited potential as antimicrobial agents due to insufficient water solubility or inadequate stability in aqueous solution.…”

Section: Introductionmentioning

confidence: 99%

“…In other efforts to obtain strong antimicrobial agents, metal ions such as Ni(II) and Cu(II) ions are coordinated to already known antibiotic sulfonamides and found to increase the apparent antimicrobial activity overall. , However, as the activity of many complexes remains outside of the susceptibility range toward bacteria (minimum inhibitory concentration, MIC ≤ 32 or 16 μg/mL) at unknown cytotoxicity toward human cells, metal complexes are often precluded from further consideration as effective antimicrobial agents. Nevertheless, a recent systematic screening of metal complexes from a 960-member library disclosed 88 complexes in the susceptibility range of selected Gram-positive and Gram-negative bacteria . Among the active and not toxic complexes, inorganic coordination compounds derived from Pt, Ag, Pd, Ir, and Cu are frequently observed …”

Section: Introductionmentioning

confidence: 99%

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Structure–Activity-Relationship Studies to Elucidate Sources of Antibacterial Activity of Modular Polyacrylate Microgels

Clem

Sharma

Striegler

2021

ACS Appl. Bio Mater.

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Emerging infections of unknown origin and increasing bacterial resistance against available antibiotics necessitate the development of different antimicrobial agents with unconventional mechanisms of action. A promising strategy to meet this need may be found by combining polymeric scaffolds with transition metals, e.g., by decorating polyacrylate-based microgels with Cu(II) complexes. A series of structure−activity relationship studies using broth microdilution assays with such materials and Staphylococcus aureus concluded that the antimicrobial activity of microgels can be tailored during their synthesis by choice of co-monomers, by design of the binding strength between Cu(II) ions and backbone ligands, and by selection of the counter ions for coordination to the metal complexes. A microgel Cu 2 L P(EG) (L = VBbsdpo) with an optimized minimal inhibitory concentration of 0.39 ± 0.03 μg/mL is thereby derived and synthesized from 60 mol % of cross-linking ethylene glycol dimethacrylate, 40 mol % butyl acrylate, 0.5 mol % VBbsdpo ligand with 1 mol % Cu(II) ions, and 5 mol % ethylene glycol as counter ions. The antimicrobial activity of the microgel has a lifetime of over 18 months at ambient temperature. Bactericidal activity of the same microgel is observed by replating assays in less than 15 min when exposing S. aureus to microgel concentrations of 1.5-fold of its minimum inhibitory concentration (MIC) value or higher. Furthermore, spectrophotometric evaluations at 260 nm revealed time-and concentration-dependent release of intracellular bacterial components after interactions with the microgel indicating irreversible damage to the bacterial cell membrane as a possible mechanism of activity. Preliminary results indicate that the selected microgels are not cytotoxic toward human dermal fibroblasts at MIC value concentrations for over 20 h.

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Correction: Metal complexes as a promising source for new antibiotics

Abstract: Correction for ‘Metal complexes as a promising source for new antibiotics’ by Angelo Frei et al., Chem. Sci., 2020, 11, 2627–2639.

Cited by 7 publications

References 0 publications

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy

In vitro antibacterial activity of dinuclear thiolato-bridged ruthenium(II)-arene compounds

Structure–Activity-Relationship Studies to Elucidate Sources of Antibacterial Activity of Modular Polyacrylate Microgels

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