The synthesis and antibacterial activity study of ruthenium-based metallodrugs with a membrane-disruptive mechanism against <i>Staphylococcus aureus</i>

Chen, Yushou; Liu, Lianghong; Wang, xuerong; Liao, Zhouyuji; Wang, Runbin; Xiong, Yan‐Shi; Chen, Jianxin; Jiang, Guijuan; Wang, Jintao; Liao, Xiangwen

doi:10.1039/d2dt01531e

Cited by 16 publications

(15 citation statements)

References 42 publications

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“…Over the past decade, numerous organic and inorganic nanomaterials have emerged as a new generation of antibacterial agents with no drug resistance. 3,4 Although each nanomaterial has its own unique antibacterial mode, several general antimicrobial strategies have been widely recognized, which work independently or in combination. The first modality involves the exceptional toxicity of some active metal ions, such as Ag + and Cu 2+ , to the cell membrane, protein, and DNA of microorganisms.…”

Section: Introductionmentioning

confidence: 99%

A bioinspired polydopamine–FeS nanocomposite with high antimicrobial efficiency via NIR-mediated Fenton reaction

Huang

Shi

et al. 2023

Dalton Trans.

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Section: Introductionmentioning

confidence: 99%

A bioinspired polydopamine–FeS nanocomposite with high antimicrobial efficiency via NIR-mediated Fenton reaction

Huang

Shi

et al. 2023

Dalton Trans.

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“…[ 82 ] Therefore, once the structural integrity of the bacterial cell membrane is disrupted, the bacteria will die rapidly. [ 83 ] This mechanism is also exploited to treat osteomyelitis.…”

Section: Bacterial Cell Membrane‐targeting Strategiesmentioning

confidence: 99%

Flourishing Antibacterial Strategies for Osteomyelitis Therapy

et al. 2023

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Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long-term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti-infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.

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“…Recently, the encouraging results obtained in the design of antitumoral agents − have renewed the interest in Ru(II)-polypyridyl complexes (RPCs), a versatile class of compounds whose antibacterial potential was first reported over 70 years ago. , Their rich chemical–physical repertoire, which includes versatile optical and luminescent properties, capacity to interact with key biological targets, and amenability to synthetic tailoring (just to name a few), has been indeed exploited to develop new classes of antibacterial agents. − Of particular relevance is the combination of RPCs with light in the so-called antimicrobial photodynamic therapy (aPDT), − a technique that relies on the irradiation of a photosensitizer (RPCs) to promote the generation of highly cytotoxic reactive oxygen species (ROS). − Besides ROS sensitization, whose effectiveness against both sensitive and multidrug-resistant bacteria has been reported, , the main advantage of aPDT consists in the complete spatiotemporal control over the drug activation, which offers the important chance to overcome overdose and side effect issues normally associated with the systemic administration of antimicrobials. However, the reliance of aPDT on molecular oxygen still threatens its application to hypoxic environments, such as anaerobic infections .…”

Section: Introductionmentioning

confidence: 99%

Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions

et al. 2023

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Ruthenium(II) polypyridyl complexes (RPCs) are gaining momentum in photoactivated chemotherapy (PACT), thanks to the possibility of overcoming the classical reliance on molecular oxygen of photodynamic therapy while preserving the selective drug activation by using light. However, notwithstanding the intriguing perspectives, the translation of such an approach in the development of new antimicrobials has been only barely considered. Herein, MTZH-1 and MTZH-2, two novel analogues of metronidazole (MTZ), a mainstay drug in the treatment of anaerobic bacterial infections, were designed and inserted in the strained ruthenium complexes [Ru(tpy)(dmp)(MTZ-1)]PF6 (Ru2) and [Ru(tpy)(dmp)(MTZ-2)]PF6 (Ru3) (tpy = terpyridine, dmp = 2,9-dimethyl-1,10-phenanthroline) (Chart 1). Analogously to the parental compound [Ru(tpy)(dmp)(5NIM)]PF6 (Ru1) (5-nitroimidazolate), the Ru(II)-imidazolate coordination of MTZ derivatives resulted in promising Ru(II) photocages, capable to easily unleash the bioactive ligands upon light irradiation and increase the antibacterial activity against Bacillus subtilis, which was chosen as a model of Gram-positive bacteria. The photoreleased 5-nitroimidazole-based ligands led to remarkable phototoxicities under hypoxic conditions (<1% O2), with the lead compound Ru3 that exhibited the highest potency across the series, being comparable to the one of the clinical drug MTZ. Besides, the chemical architectures of MTZ derivatives made their interaction with NimAunfavorable, being NimA a model of reductases responsible for bacterial resistance against 5-nitroimidazole-based antibiotics, thus hinting at their possible use to combat antimicrobial resistance. This work may therefore provide fundamental knowledge in the design of novel photoresponsive tools to be used in the fight against infectious diseases. For the first time, the effectiveness of the “photorelease antimicrobial therapy” under therapeutically relevant hypoxic conditions was demonstrated.

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The synthesis and antibacterial activity study of ruthenium-based metallodrugs with a membrane-disruptive mechanism against Staphylococcus aureus

Abstract: The wide spread of drug-resistant bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), have posed a tremendous threat to global health. Of particular concern, resistance to vancomycin, linezolid and daptomycin have already...

Cited by 16 publications

References 42 publications

A bioinspired polydopamine–FeS nanocomposite with high antimicrobial efficiency via NIR-mediated Fenton reaction

A bioinspired polydopamine–FeS nanocomposite with high antimicrobial efficiency via NIR-mediated Fenton reaction

Flourishing Antibacterial Strategies for Osteomyelitis Therapy

Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions

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