Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus

Yang, Xun-Cai; Zeng, Chunmei; Avula, Srinivasa Rao; Peng, Xin-Mei; Geng, Rong‐Xia; Zhou, Cheng‐He

doi:10.1016/j.ejmech.2022.114891

Cited by 54 publications

(38 citation statements)

References 48 publications

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“…The generation of reactive oxygen species (ROS) in normal cells is balanced with the cellular antioxidant system comprising of chief antioxidant enzymes. , Due to some external factors, such as antibiotic interference, the antioxidant detoxification process collapses, which results in ROS surge and oxidative stress as the one responsible for biomolecule damage such as lipids, proteins, and DNA, and induction of bacterial dysfunction, even apoptosis. − This study used fluorescent probe DCFH-DA to monitor the ROS of P. A. treated with ATQ 17a . The green fluorescent intensity showed a dose-dependent escalation in Figure S13, which distinctly perceived that the active 3-(aminothiazolyl)quinolone 17a could induce ROS accumulation and further oxidative stress to burden the bacteria.…”

Section: Results and Discussionmentioning

confidence: 99%

New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential

Zhang

Battini

et al. 2023

J. Agric. Food Chem.

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New antibacterial 3-(aminothiazolyl)quinolones (ATQs) were designed and efficiently synthesized to counteract the growing multidrug resistance in animal husbandry. Bioactive assays manifested that N,N-dicyclohexylaminocarbonyl ATQ 10e and methyl ATQ 17a, respectively, showed better antibacterial behavior against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa than reference drug norfloxacin. Notably, highly active ATQ 17a with low hemolysis, negligible mammalian cytotoxicity, and good pharmacokinetic properties displayed low trends to induce resistance and synergistic combinations with norfloxacin. Preliminary mechanism exploration implied that representative ATQ 17a could inhibit the formation of biofilms and destroy bacterial membrane integrity, further binding to intracellular DNA and DNA gyrase to hinder bacterial DNA replication. ATQ 17a could also induce the production of excess reactive oxygen species and reduce bacterial metabolism to accelerate bacterial death. These results provided a promise for 3-(aminothiazolyl)quinolones as new potential multitargeting antibacterial agents to treat bacterial infection of animals.

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Section: Results and Discussionmentioning

confidence: 99%

New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential

Zhang

Battini

et al. 2023

J. Agric. Food Chem.

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“…The vigorous growth of bacteria cannot be separated from metabolic activities. Metabolic activity has emerged as a new focus and has been applied in the research studies on anti-microorganism to explain the possible mechanism. , Thence, alamar blue was employed as redox indicator to evaluate the cellular metabolic activity . The metabolic activity decreased with the increase of triazolyl PD 7a in Figure , revealing that compound 7a could suppress the growth of A.…”

Section: Resultsmentioning

confidence: 99%

Azolylpyrimidinediols as Novel Structural Scaffolds of DNA-Groove Binders against Intractable Acinetobacter baumannii

Tan

Wang

et al. 2023

J. Med. Chem.

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A unique class of antibacterial azolylpyrimidinediols (APDs) and their analogues were developed. Some synthesized compounds showed excellent bacteriostatic potency; especially, triazolylpyrimidinediol (triazolyl PD) 7a exhibited good anti-Acinetobacter baumannii potential with a low MIC of 0.002 mmol/ L. Triazolyl PD 7a with inconspicuous cytotoxicity and hemolytic activity could eradicate the established biofilm, showed low resistance, and exhibited favorable drug-likeness. Mechanistic explorations revealed that compound 7a without membrane-targeting ability could decrease metabolic activity, interact with DNA through groove binding action to block DNA replication rather than intercalate into and cleave DNA, and thus inhibit bacterial growth. Further computations displayed that the low E HOMO and large energy gap might help triazolyl PD 7a binding to biological targets more easily. Moreover, compound 7a gave appreciable in vivo pharmacokinetic properties and pharmacodynamics. These findings of azolylpyrimidinediols as novel structural scaffolds of DNA-groove binders might imply a large promise for the treatments of Acinetobacter baumannii infection.

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“…The activity of intracellular GSH was determined using standard Ellman’s assay [ 61 ]. Then, 10 6 CFU/mL of Candida tropicalis was treated with increasing concentrations of compound 7f for 6 h at 37 °C and 200 rpm.…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments

2022

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The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including Aspergillus fumigatus, Candida tropicalis and Candida parapsilosis 22019. Especially, thioether benzimidazole derivative 7f with excellent anti-Candida tropicalis efficacy (MIC = 4 μg/mL) possessed low cytotoxicity, safe hemolysis level and less susceptibility to induce resistance. Biochemical interactions displayed that 7f could form a supramolecular complex with DNA to block DNA replication, and constitute a biosupermolecule with cytochrome P450 reductase (CPR) from Candida tropicalis to hinder CPR biological function. Additionally, 7f presented strong lipase affinity, which facilitated its permeation into cell membrane. Moreover, 7f with dynamic antifungal potency promoted the production and accumulation of reactive oxygen species (ROS) in cells, which destroyed the antioxidant defence system, led to oxidative stress with lipid peroxidation, loss of glutathione, membrane dysfunction and metabolic inactivation, and eventually caused cell death. The chemical and dynamic antifungal synergistic effect initiated by hydroxyethyl naphthalimides was a reasonable treatment window for prospective development.

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Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus

Cited by 54 publications

References 48 publications

New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential

New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential

Azolylpyrimidinediols as Novel Structural Scaffolds of DNA-Groove Binders against Intractable Acinetobacter baumannii

Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments

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