Development of ruthenium(ii) complexes as topical antibiotics against methicillin resistant Staphylococcus aureus

Lam, P. L.; Lü, Guo-Liang; Hon, Karen; Lee, K.-W.; Ho, Cheuk Lam; Wang, X.; Tang, Johnny; Lam, Kim Hung; Wong, Raymond Pui On; Kok, Stanton Hon Lung; Bian, Zhaoxiang; Li, H.; Lee, K. K.-H.; Gambari, Roberto; Chui, Chung Hin; Wong, Wai‐Yeung

doi:10.1039/c3dt52879k

Cited by 63 publications

(41 citation statements)

References 36 publications

(54 reference statements)

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“…13 [Ru(bpy) 2 (NPDA)] 2+ (NPDA = N -phenyl-substituted diazofluorene) is active against methicillin-resistant S. aureus (MRSA) and generates ROS to kill MRSA. 14 Some dinuclear Ru( ii ) complexes have been studied, where rigid linkers between metal centers show lower activity against S. aureus and E. coli compared to flexible linkers. 15 The activity appeared to be linked to lipophilicity, as increased lipophilicity results in increased penetration through cell membranes and therefore increased uptake.…”

Section: Introductionmentioning

confidence: 99%

Combatting AMR: photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Combatting AMR: photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

et al. 2017

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“…Several other N−N ruthenium(II) complexes have also been shown to permeabilize bacterial membranes . However, other antibacterial ruthenium(II) complexes have been shown to produce reactive oxygen species (ROS), interact with proteins or bind to nucleic acids (DNA,, and RNA). As such, the exact biological mode of action of the known ruthenium(II) antibacterial complexes has still not been completely elucidated .…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterisation and Antimicrobial Studies of some 2,6‐bis(1,2,3‐Triazol‐4‐yl)Pyridine Ruthenium(II) “Click” Complexes

et al. 2019

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A family of homo-and hetero-leptic ruthenium(II) bis-tridentate complexes generated from 2,6-bis(1-R-1,2,3triazol-4-yl)pyridine "click" ligands (R-tripy) with either aliphatic or aromatic substituents were synthesized (35-97%).The family of compounds were tested for antimicrobial activity in vitro against both Staphylococcus aureus (S. aureus, ATCC 25923) and Escherichia coli (E. coli, ATCC 25922) bacteria. The antibacterial activity showed dependence on the alkyl chain length of the [Ru(R-tripy) 2 ] 2 + (Cl À ) 2 complexes, with the best activity occurring for the three complexes featuring either hexyl or heptyl substituents on the ligands. The minimum inhibitory concentrations (MICs) for the most active mononuclear complex [Ru(hexyltripy)(heptyltripy)] 2 + (Cl À ) 2 were 2 μg/mL and 8 μg/mL respectively against S. aureus and E. coli. The three most active complexes were screened against other pathogenic bacteria, including two strains of Methicillin resistant S. aureus (MRSA). The compounds showed good activity against the Gram positive strains (MIC = 4-8 μg/mL) but were less effective against Gram negative bacteria (MIC = 8-16 μg/mL). Cytotoxicity experiments with eukaryotic cells lines (cancer and skin) suggested that the R-tripy ligands and complexes were reasonably cytotoxic (IC 50 = 2-25 μM) and displayed little to no selectivity for bacteria over eukaryotic cells lines.[a] Q. /phen ligands and have been used to develop metal complexes for a range of applications. [19] Two of the complexes ([Ru(hexpytri) 3 ] 2 + and [Ru(octpytri) 3 ] 2 + (where hexpytri = 2-(1hexyl-1H-1,2,3-triazol-4-yl)pyridine and octpytri = 2-(1-octyl-1H-1,2,3-triazol-4-yl)pyridine) showed good antimicrobial activity against Gram positive S. aureus and MRSA (MICs = 1-8 μg/mL) but little to no activity against Gram negative bacteria (MIC = 16-> 128 μg/mL). The mer and fac isomers of the complexes showed no difference in activity. Propidium iodide assays and transmission electron microscopy (TEM) indicated that the main mode of action for these ruthenium(II) R-pytri complexes was cytoplasmic membrane disruption.Building on that work, herein we report the synthesis of a structurally related family of ruthenium(II) "click" complexes generated from tridentate 2,6-bis(1-R-1H-1,2,3-triazol-4-yl) pyridine (R-tripy) ligands (Scheme 1). The new bis-tridentate ruthenium(II) complexes, [Ru(R-tripy) 2 ] 2 + (Cl À ) 2 , retain most of the structural features of the previously studied [Ru(R-pytri) 3 ] 2 + (X À ) 2 complexes but they do not form isomers (either enantiomers or diastereomers). The new "click" complexes were tested for antimicrobial activity in vitro against both S. aureus and Escherichia coli (E. coli) bacteria. Additionally, the cytotoxicity of the most active complexes was examined against three human cell lines. Results and DiscussionSynthesis of Tridentate 2,6-bis(1-R-1,2,3-triazol-4-yl)pyridine (R-tripy) Ligands . TEM images a) untreated S. aureus b) S. aureus incubated with 4 μg/mL of [Ru(hexyltripy)(heptyltripy)] 2 + , c) and d) S...

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“…Recently Ru(II) complexes [Ru(L 14 )(bpy) 2 ](PF 6 ) 2 (where L 14 is a 4,5-diazafluoren-9-imine ligand with various N-aryl groups) have been found to be effective topical antibiotics against the bacteria Staphylococcus aureus which is resistant to the antibiotic methicillin. 167 In particular the derivative with a -OC 7 H 15 group attached to the N-aryl group, which is nontoxic toward human skin keratinocyte cells, exhibits strong microbicidal and bacterial growth inhibitory effects. 167 One possible mechanism, for how these Ru(II) complexes are active against S. aureus, is through the generation of reactive oxygen species.…”

Section: Iii4 Bioinorganic Chemistry Of 45-diazafluorene Derivativesmentioning

confidence: 99%

Coordination chemistry and applications of versatile 4,5-diazafluorene derivatives

Annibale

Song

2016

Dalton Trans.

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This perspective review will examine the coordination chemistry and applications of metal complexes of 4,5-diazafluorene derivatives. The versatile derivatives of 4,5-diazafluorene can serve multiple roles, and display a number of coordination modes. The ambidentate derivatives with multiple coordination sites can allow for the syntheses of coordination polymers, multimetallic, and macrocyclic complexes. In addition, certain 4,5-diazafluorene derivatives can serve as spectator ligands to support reactivity at the metal centre, or as reactive actor ligands engaging in atypical reactivity patterns. The applications of metal complexes of 4,5-diazafluorene derivatives in catalysis, photochemistry and photophysics, as well as in bioinorganic chemistry are also surveyed.

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Development of ruthenium(ii) complexes as topical antibiotics against methicillin resistant Staphylococcus aureus

Cited by 63 publications

References 36 publications

Combatting AMR: photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

Combatting AMR: photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

Synthesis, Characterisation and Antimicrobial Studies of some 2,6‐bis(1,2,3‐Triazol‐4‐yl)Pyridine Ruthenium(II) “Click” Complexes

Coordination chemistry and applications of versatile 4,5-diazafluorene derivatives

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