Discovery of novel nitroimidazole enols as Pseudomonas aeruginosa DNA cleavage agents

Li, Zhenzhen; Goodla, Lavanya; Tangadanchu, Vijai Kumar Reddy; Gao, Wei‐Wei; Zhou, Cheng‐He

doi:10.1016/j.bmc.2017.10.028

Cited by 43 publications

(13 citation statements)

References 56 publications

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“…As a signal molecule between bacterial cells, indole is an important component of tryptophan (an amino acid that is used in the biosynthesis of proteins), it plays a mediating role in many biological processes [12] . In addition, owning to its electron‐rich structure, there are many possible reaction sites of indole skeleton.…”

Section: Introductionmentioning

confidence: 99%

“…[10,11] As a signal molecule between bacterial cells, indole is an important component of tryptophan (an amino acid that is used in the biosynthesis of proteins), it plays a mediating role in many biological processes. [12] In addition, owning to its electron-rich structure, there are many possible reaction sites of indole skeleton. At present, the medicinal value of indole derivatives is derived from their anti-inflammatory, anticancer, and antihistaminic properties, as well as other applications.…”

Section: Introductionmentioning

confidence: 99%

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Novel Schiff Base‐conjugated para‐Aminobenzenesulfonamide Indole Hybrids as Potentially Muti‐targeting Blockers against Staphylococcus aureus

Zhang

Huang

et al. 2022

Asian J Org Chem

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Staphylococcus aureus (S. aureus) has developed strong resistance to a variety of clinical antibiotics, which makes the design and synthesis of novel structural molecules with outstanding antibacterial potential put on the agenda. The results of bioactivity assessment displayed that sulfonamide indole compound 4 h, which was modified with a butene group, had remarkable antibacterial activity against S. aureus (MIC=5 μM), and was superior to the reference drugs norfloxacin (MIC=13 μM) and sulfathiazole (MIC=501 μM). The propensity of evaluation of hybrid 4 h to induce drug resistance was lower than that of the reference drugs. In addition, the cytotoxicity assay revealed that compound 4 h had no obvious cytotoxicity to normal mammalian cells (RAW 264.7). Molecular docking analysis further demonstrated that the highly active molecule 4 h could interact with the active sites of DNA hexamer duplex and human carbonic anhydrase isozyme II through hydrogen bonds. Moreover, preliminary mechanistic studies indicated that hybrid 4 h prospectively acted as an blocker by disrupting the bacterial membrane of S. aureus and inserting itself into S. aureus DNA to prevent strains from replicating.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Schiff Base‐conjugated para‐Aminobenzenesulfonamide Indole Hybrids as Potentially Muti‐targeting Blockers against Staphylococcus aureus

Zhang

Huang

et al. 2022

Asian J Org Chem

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“…Heterocyclic azoles are helpful structural fragments for biological activity and extensively used in drug design and development because they could easily interact with the active sites of organisms through noncovalent interactions, like coordination bond, hydrogen bond, π–π stacking, etc., to improve the physicochemical and pharmacokinetic properties, thus improving their bioavailability and target selectivity. − In particular, five-membered azoles, such as imidazole, − triazole, − and tetrazole, , played an important role in the field of medicine, and some azole compounds have been successfully used in clinic like antibacterial secnidazole and ornidazole as well as antifungal fluconazole and voriconazole. − This further promotes increasing effort toward fused azoles, including benzimidazole, − benzotriazole, and carbazole, − and some fused azoles, like carbazomycins and murrayafoline, have been marketed. − …”

Section: Introductionmentioning

confidence: 99%

Sulfonamide-Derived Four-Component Molecular Hybrids as Novel DNA-Targeting Membrane Active Potentiators against Clinical Escherichia coli

Bheemanaboina

Battini

et al. 2019

Mol. Pharmaceutics

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Novel sulfonamide-based four-component molecular hybrids as potential DNA-targeting antimicrobial agents were developed from marketed acetanilide through convenient procedures. Biological assays indicated that a few of the target compounds showed significant inhibitory efficiencies toward the tested bacteria and fungi. Noticeably, metronidazole hybrid 6a exhibited a lower minimum inhibitory concentration (MIC) value of 0.019 mM against clinical drug-resistant Escherichia coli (E. coli), which showed to be 84-fold more active than clinical norfloxacin and had no obvious toxicity toward human breast cancer MCF-7 cells. Synergistic combinations of compound 6a with clinical antibacterial or antifungal drugs could improve the antimicrobial efficiency. Further molecular modeling indicated that the active molecule 6a could bind with THR-199, HIS-64, and GLN-92 residues of human carbonic anhydrase isozyme II through hydrogen bonds and was also able to insert into base-pairs of the DNA hexamer duplex by forming hydrogen bonds. The preliminary exploration of the antibacterial mechanism suggested that compound 6a was capable of disturbing the E. coli membrane effectively and intercalating into clinical resistant E. coli bacterial DNA through noncovalent bonds to form a supramolecular complex, thus exerting its powerful antimicrobial activity. This might suggest a great possibility for hybrid 6a to be a DNA-targeting membrane active potentiator against clinical drug-resistant E. coli.

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“…In fact, satisfactory antimicrobial activity of this type of conjugates had already been highlighted [81]. Furthermore, it was kept in mind that α,β-unsaturated carbonyl derivatives are linkers commonly used as functional structures for drug design [82].…”

Section: It Was Then Found That 2-mentioning

confidence: 97%

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

Rossi

Ciofalo

2020

Molecules

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The rapid growth of serious infections caused by antibiotic resistant bacteria, especially the nosocomial ESKAPE pathogens, has been acknowledged by Governments and scientists and is one of the world’s major health problems. Various strategies have been and are currently investigated and developed to reduce and/or delay the bacterial resistance. One of these strategies regards the design and development of antimicrobial hybrids and conjugates. This unprecedented critical review, in which our continuing interest in the synthesis and evaluation of the bioactivity of imidazole derivatives is testified, aims to summarise and comment on the results obtained from the end of the 1900s until February 2020 in studies conducted by numerous international research groups on the synthesis and evaluation of the antibacterial properties of imidazole-based molecular hybrids and conjugates in which the pharmacophoric constituents of these compounds are directly covalently linked or connected through a linker or spacer. In this review, significant attention was paid to summarise the strategies used to overcome the antibiotic resistance of pathogens whose infections are difficult to treat with conventional antibiotics. However, it does not include literature data on the synthesis and evaluation of the bioactivity of hybrids and conjugates in which an imidazole moiety is fused with a carbo- or heterocyclic subunit.

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Discovery of novel nitroimidazole enols as Pseudomonas aeruginosa DNA cleavage agents

Cited by 43 publications

References 56 publications

Novel Schiff Base‐conjugated para‐Aminobenzenesulfonamide Indole Hybrids as Potentially Muti‐targeting Blockers against Staphylococcus aureus

Novel Schiff Base‐conjugated para‐Aminobenzenesulfonamide Indole Hybrids as Potentially Muti‐targeting Blockers against Staphylococcus aureus

Sulfonamide-Derived Four-Component Molecular Hybrids as Novel DNA-Targeting Membrane Active Potentiators against Clinical Escherichia coli

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

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