Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant <i>Pseudomonas aeruginosa</i> DNA

Wang, Yanan; Bheemanaboina, Rammohan R. Yadav; Gao, Wei‐Wei; Kang, Jie; Cai, Gui‐Xin; Zhou, Cheng‐He

doi:10.1002/cmdc.201700739

Cited by 52 publications

(23 citation statements)

References 58 publications

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“…153 Benzimidazole-quinoline hybrids (e.g., 43; Fig 5; MIC of 1 µg/mL) do not intercalate into DNA isolated from drugresistant P. aeruginosa but are able to cleave DNA effectively. 154 Anti-Mtb activity (MIC of 0.12 µg/mL) has been also reported for coumarin-theophylline hybrids (44; Fig. 5).…”

Section: Molecular Hybridizationsupporting

confidence: 54%

“…Benzimidazole-quinoline hybrids (e.g., 43 ; Fig 5 ; MIC of 1 µg/mL) do not intercalate into DNA isolated from drug-resistant P. aeruginosa but are able to cleave DNA effectively. 154…”

Section: Old Structures: Delaying the Amrmentioning

confidence: 99%

“…Based on molecular modeling studies, these series of compounds appears to be DNA gyrase inhibitors. 150 As a continuation of earlier studies on quinolonecontaining hybrids with activity against both gram-positive and gram-negative organisms, 151 quinolone-thiourea, 152 quinoline-oxadiazole, 153 and quinolone-benzimidazole 154 hybrids have been prepared. In the former series, MICs of 41 (Fig.…”

Section: Molecular Hybridizationmentioning

confidence: 99%

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Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Konaklieva

2019

SLAS Discovery

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Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new scaffolds have emerged. The effectiveness of antibiotics, however, is in sharp decline because of the emergence of drug-resistant microorganisms. The prevalence of drug resistance, both in clinical and community settings, is a consequence of bacterial ingenuity in altering pathways and/or cell morphology, making it a persistent threat to human health. The fundamental ability of pathogens to survive in a multitude of habitats can be triggered by recognition of chemical signals that warn organisms of exposure to a potentially harmful environment. Host immune defenses, including reactive oxygen intermediates and antibacterial substances, are among the multitude of chemical signals that can subsequently trigger expression of phenotypes better adapted for survival in that hostile environment. Thus, resistance development appears to be unavoidable, which leads to the conclusion that developing an alternative perspective for treatment options is vital. This review will discuss emerging medicinal chemistry approaches for addressing the global multidrug resistance in the 21st century.

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Section: Molecular Hybridizationsupporting

confidence: 54%

“…Benzimidazole-quinoline hybrids (e.g., 43 ; Fig 5 ; MIC of 1 µg/mL) do not intercalate into DNA isolated from drug-resistant P. aeruginosa but are able to cleave DNA effectively. 154…”

Section: Old Structures: Delaying the Amrmentioning

confidence: 99%

Section: Molecular Hybridizationmentioning

confidence: 99%

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Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Konaklieva

2019

SLAS Discovery

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“…One of the compounds showed unusual activity on the resistant strains of Pseudomonas aeruginosa and Candida tropicalis strains. It also caused a decrease in the resistance of Pseudomonas aeruginosa , compared to norfloxacin [ 277 ].…”

Section: Compounds In Development Based On Antibacterial Qns Structuresmentioning

confidence: 99%

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

et al. 2021

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The evolution of the class of antibacterial quinolones includes the introduction in therapy of highly successful compounds. Although many representatives were withdrawn due to severe adverse reactions, a few representatives have proven their therapeutical value over time. The classification of antibacterial quinolones into generations is a valuable tool for physicians, pharmacists, and researchers. In addition, the transition from one generation to another has brought new representatives with improved properties. In the last two decades, several representatives of antibacterial quinolones received approval for therapy. This review sets out to chronologically outline the group of approved antibacterial quinolones since 2000. Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. These compounds have been characterized regarding physicochemical properties, formulations, antibacterial activity spectrum and advantageous structural characteristics related to antibacterial efficiency. At present these new compounds (with the exception of nadifloxacin) are reported differently, most often in the fourth generation and less frequently in a new generation (the fifth). Although these new compounds’ mechanism does not contain essential new elements, the question of shaping a new generation (the fifth) arises, based on higher potency and broad spectrum of activity, including resistant bacterial strains. The functional groups that ensured the biological activity, good pharmacokinetic properties and a safety profile were highlighted. In addition, these new representatives have a low risk of determining bacterial resistance. Several positive aspects are added to the fourth fluoroquinolones generation, characteristics that can be the basis of the fifth generation. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research.

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“…Various biological processes of bioactive molecules including transportation, distribution, or metabolism depend on their lipophilic properties [37]. The bioactivity of target molecules can be predicted using the calculated lipid/water partition coefficients (ClogP) [38]. To further study the physical and chemical properties of new salts, the values of ClogP for all imidazolium cations were calculated using ChemBioOffice 2012, and the obtained results are shown in Table 4.…”

Section: Effect Of Clogp Values On Antimicrobial Activitymentioning

confidence: 99%

Steroid-Functionalized Imidazolium Salts with an Extended Spectrum of Antifungal and Antibacterial Activity

Malinowska

Sawicka

Niemirowicz-Laskowska

et al. 2021

IJMS

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It is established that high rates of morbidity and mortality caused by fungal infections are related to the current limited number of antifungal drugs and the toxicity of these agents. Imidazolium salts as azole derivatives can be successfully used in the treatment of fungal infections in humans. Steroid-functionalized imidazolium salts were synthesized using a new, more efficient method. As a result, 20 salts were obtained with high yields, 12 of which were synthesized and characterized for the first time. They were derivatives of lithocholic acid and 3-oxo-23,24-dinorchol-4-ene-22-al and were fully characterized by 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high resolution mass spectrometry (HRMS). Due to the excellent activity against bacteria and Candida albicans, new research was extended to include tests on five species of pathogenic fungi and molds: Aspergillus niger ATCC 16888, Aspergillus fumigatus ATCC 204305, Trichophyton mentagrophytes ATCC 9533, Cryptococcus neoformans ATCC 14116, and Microsporum canis ATCC 11621. The results showed that the new salts are almost universal antifungal agents and have a broad spectrum of activity against other human pathogens. To initially assess the safety of the synthesized salts, hemocompatibility with host cells and cytotoxicity were also examined. No toxicity was observed at the concentration at which the compounds were active against pathogens.

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Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Cited by 52 publications

References 58 publications

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

Steroid-Functionalized Imidazolium Salts with an Extended Spectrum of Antifungal and Antibacterial Activity

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