Synthesis, conformational analysis and antibacterial activity of Au(<scp>i</scp>)–Ag(<scp>i</scp>) and Au(<scp>i</scp>)–Hg(<scp>ii</scp>) heterobimetallic N-heterocyclic carbene complexes

Li, Zili; Mackie, Emily R. R.; Ramkissoon, Pria; Mather, Joel C; Wiratpruk, Nuchareenat; Costa, Tatiana P. Soares da; Barnard, Peter J.

doi:10.1039/d0dt02225j

Cited by 12 publications

(14 citation statements)

References 81 publications

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“…The 1 H-NMR spectra of 5a–5c displayed sharp signals and a singlet peak corresponding to the ethylene linker group protons at 4.85, 4.98 and 4.92 ppm for 5a , 5b and 5c respectively, contrasting to recently reported methylene linked dinuclear complexes of imidazolylidene ligands where the methylene protons appeared as two broad doublet signals. 43 Complex 5b (Fig. 4) crystallises in the triclinic space group P 1̄ and the cation shows an Au⋯Au distance of 3.5727(3) Å, with the average of the Au–C carbene bond distances being 2.020 Å. Interactions between the gold( i ) centres and the bromide counter ions are apparent with the distances being 3.7512(7) Å and 3.5185(7) Å for Au(1)–Br(1) and Au(2)–Br(2) respectively, with hydrogen bonding interactions also apparent.…”

Section: Resultsmentioning

confidence: 99%

“…23,44 The dinuclear gold( i ) complexes ( 5a and 5b ) displayed no significant antibacterial activity against all of the strains tested, consistent with recently published work by our group on similar imidazolylidene based dinuclear gold( i ) complexes. 43 The lack of anti-bacterial activity for 5a and 5b may result from the dicationic charge of these complexes causing poor uptake into bacterial cells by passive diffusion, however additional studies are required to confirm this hypothesis.…”

Section: Resultsmentioning

confidence: 99%

“…The dinuclear gold( i ) complexes 5a and 5b displayed little or no antibacterial activity, in agreement with recently reported results. 43…”

Section: Discussionmentioning

confidence: 99%

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Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes

et al. 2022

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“…53,54 Serial dilutions of 2,6-PDC were prepared in 96-well microplates using tryptic soy broth as the diluent. 55,56 Plates were inoculated with 1 × 10 5 colony forming units per mL of bacteria and incubated at 25 □ for 20 h. Growth was assessed by measuring the absorbance at 600 nm and the lowest concentration of inhibitor with no observable growth determined to be the MIC value. 55,56 Experiments were performed in biological triplicates.…”

Section: Methodsmentioning

confidence: 99%

From bacteria to plants: a repurposing strategy in the pursuit for novel herbicides

Mackie

Barrow

Giel

et al. 2022

Preprint

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Herbicide resistance represents one of the biggest threats to our natural environment and agricultural sector. Thus, new herbicides are urgently needed to tackle the rise in herbicide-resistant weeds. Here, we employed a novel strategy to repurpose a ′failed′ antibiotic into a new and target-specific herbicidal compound. Specifically, we identified an inhibitor of bacterial dihydrodipicolinate reductase (DHDPR), an enzyme involved in lysine biosynthesis in plants and bacteria, that exhibited no antibacterial activity but severely attenuated germination of the plant Arabidopsis thaliana. We confirmed that the inhibitor targets plant DHDPR orthologues in vitro, and exhibits no toxic effects against human cell lines. A series of analogues were then synthesised with improved efficacy in germination assays and against soil-grown A. thaliana plants. We also showed that our lead compound is the first lysine biosynthesis inhibitor with herbicidal activity against a weed species, providing proof-of-concept that DHDPR inhibition may represent a much-needed new herbicide mode of action. Furthermore, this study exemplifies the untapped potential of repurposing ′failed′ antibiotic scaffolds to fast-track the development of herbicide candidates targeting the respective plant enzymes to combat the global rise in herbicide-resistant weeds.

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“…Antibacterial assays. The MIC for PMSH was determined against a panel of A. baumannii strains using a broth microdilution method as described previously (46)(47)(48). Specifically, an inoculum of 1 × 10 5 colony forming units per mL was used and the testing conducted using tryptic soy broth in 96-well plates.…”

Section: Enzyme Coupled Assaymentioning

confidence: 99%

The First Inhibitor of Meso-Diaminopimelate Biosynthesis with Antibacterial Activity Against Multi-Drug Resistant Bacteria

Costa

Wyllie

Ghardi

et al. 2022

Preprint

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Antibiotic resistance represents one of the biggest threats to global health. While several of our current antibiotics target the peptidoglycan within the bacterial cell wall, only a fraction of its components has been explored for antibiotic development. A component that remains under-exploited is meso-diaminopimelate (meso-DAP), a constituent of the cross-linking peptide in Gram-negative bacteria. In this study, we employed a high throughput chemical screen to identify the first inhibitor of meso-DAP biosynthesis with antibacterial activity. Indeed, the compound was shown to have minimum inhibitory concentration values of 8–16 μg/mL against a panel of multi-drug resistant Acinetobacter baumannii strains, including those resistant to the last resort antibiotic carbapenem. Importantly, the compound targets the meso-DAP biosynthesis pathway specifically, with no off-target effects observed in human cell lines, and no resistance exhibited upon continuous treatment, under the conditions tested. Furthermore, we revealed for the first time that meso-DAP biosynthesis inhibition prevents biofilm formation and disrupts established biofilms in A. baumannii. Using a Galleria mellonella model, we showed that this compound improves survival rates against A. baumannii infection by up to 40% relative to the no treatment controls. Lastly, we determined that the inhibitor potentiates the activity of several antibiotic classes, including carbapenems. Thus, this study provides proof-of-concept that meso-DAP biosynthesis represents a promising target for the development of standalone antibacterial agents with a new mode of action as well as adjuvants to be used in combinatorial regimens to rejuvenate our current antibiotic arsenal to combat resistance.

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Synthesis, conformational analysis and antibacterial activity of Au(i)–Ag(i) and Au(i)–Hg(ii) heterobimetallic N-heterocyclic carbene complexes

Abstract: A post-synthetic modification and metallation procedure has been used to prepare a family of heterobimetallic Au(I)-Ag(I) and Au(I)-Hg(II) complexes featuring either symmetrical or asymmetrical bis-N-heterocyclic carbene ligands with methylene or...

Cited by 12 publications

References 81 publications

Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes

Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes

From bacteria to plants: a repurposing strategy in the pursuit for novel herbicides

The First Inhibitor of Meso-Diaminopimelate Biosynthesis with Antibacterial Activity Against Multi-Drug Resistant Bacteria

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