Azolylpyrimidinediols as Novel Structural Scaffolds of DNA-Groove Binders against Intractable <i>Acinetobacter baumannii</i>

Tan, Yi-Min; Wang, Ya; Li, Shuo; Zhang, Shaolin; Zhou, Cheng‐He

doi:10.1021/acs.jmedchem.2c02042

Cited by 25 publications

(8 citation statements)

References 70 publications

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“…DNA, a biomacromolecule, is the main target in designing DNA-targeted antibacterial agents, as it helps in controlling metabolic processes and production of protein. 51 DNA damage occurs due to increased oxidative stress in cells; since compounds 5d and 5o can disrupt the cell membrane, they can lead to induction of ROS in cells, 52 and hence the binding ability of 5d and 5o with DNA was evaluated by absorption and emission spectroscopic techniques.…”

Section: Resultsmentioning

confidence: 99%

Bacterial cell death to overcome drug resistance with multitargeting bis-naphthalimides as potent antibacterial agents against Enterococcus faecalis

Gupta,

Luxami,

Paul

2024

J. Mater. Chem. B

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Section: Resultsmentioning

confidence: 99%

Bacterial cell death to overcome drug resistance with multitargeting bis-naphthalimides as potent antibacterial agents against Enterococcus faecalis

Gupta,

Luxami,

Paul

2024

J. Mater. Chem. B

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“…Deoxyribonucleic acid (DNA), with the function of directing the synthesis of proteins and controlling metabolic processes, has been recognized as an effective drug target in the design and development of novel efficient antibacterial drugs [ 68 , 69 , 70 ]. Considering that TQ 4 possessed a large conjugated system that possibility of intercalating into DNA and the ability to easily form hydrogen bonds and π-π interactions with DNA, thereby impeding DNA replication, the interaction between TQ 4 and calf thymus DNA was studied by UV–vis and fluorescence spectroscopy [ 71 , 72 ].…”

Section: Resultsmentioning

confidence: 99%

Novel Thiazolylketenyl Quinazolinones as Potential Anti-MRSA Agents and Allosteric Modulator for PBP2a

et al. 2023

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Bacterial infections caused by methicillin-resistant Staphylococcus aureus have seriously threatened public health. There is an urgent need to propose an existing regimen to overcome multidrug resistance of MRSA. A unique class of novel anti-MRSA thiazolylketenyl quinazolinones (TQs) and their analogs were developed. Some synthesized compounds showed good bacteriostatic potency. Especially TQ 4 was found to exhibit excellent inhibition against MRSA with a low MIC of 0.5 μg/mL, which was 8-fold more effective than norfloxacin. The combination of TQ 4 with cefdinir showed stronger antibacterial potency. Further investigation revealed that TQ 4, with low hemolytic toxicity and low drug resistance, was not only able to inhibit biofilm formation but also could reduce MRSA metabolic activity and showed good drug-likeness. Mechanistic explorations revealed that TQ 4 could cause leakage of proteins by disrupting membrane integrity and block DNA replication by intercalated DNA. Furthermore, the synergistic antibacterial effect with cefdinir might be attributed to TQ 4 with the ability to induce PBP2a allosteric regulation of MRSA and further trigger the opening of the active site to promote the binding of cefdinir to the active site, thus inhibiting the expression of PBP2a, thereby overcoming MRSA resistance and significantly enhancing the anti-MRSA activity of cefdinir. A new strategy provided by these findings was that TQ 4, possessing both excellent anti-MRSA activity and allosteric effect of PBP2a, merited further development as a novel class of antibacterial agents to overcome increasingly severe MRSA infections.

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“…Compound II201 exhibited good anti- Acinetobacter baumannii potential, with a low MIC of 0.002 mmol/L. However, when the triazole group was replaced by other azoles such as benzimidazoles, imidazoles, and tetrazoles, the anti- Acinetobacter baumannii activity was significantly reduced [ 365 ].…”

Section: Imidazole-based Supermolecules As Medicinal Agentsmentioning

confidence: 99%

Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes

Tan

Zhang

et al. 2023

Pharmaceutics

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The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure is beneficial to easily bind with various inorganic or organic ions and molecules through noncovalent interactions to form a variety of supramolecular complexes with broad medicinal potential, which is being paid an increasing amount of attention regarding more and more contributions to imidazole-based supramolecular complexes for possible medicinal application. This work gives systematical and comprehensive insights into medicinal research on imidazole-based supramolecular complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and anti-inflammatory aspects as well as ion receptors, imaging agents, and pathologic probes. The new trend of the foreseeable research in the near future toward imidazole-based supramolecular medicinal chemistry is also prospected. It is hoped that this work provides beneficial help for the rational design of imidazole-based drug molecules and supramolecular medicinal agents and more effective diagnostic agents and pathological probes.

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

Cited by 25 publications

References 70 publications

Bacterial cell death to overcome drug resistance with multitargeting bis-naphthalimides as potent antibacterial agents against Enterococcus faecalis

Bacterial cell death to overcome drug resistance with multitargeting bis-naphthalimides as potent antibacterial agents against Enterococcus faecalis

Novel Thiazolylketenyl Quinazolinones as Potential Anti-MRSA Agents and Allosteric Modulator for PBP2a

Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes

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