Review of the Quinolone Family

Jacoby, George A.; Hooper, David C.

doi:10.1007/978-1-4614-1400-1_4

Cited by 11 publications

(12 citation statements)

References 198 publications

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“…Small molecules that are totally synthetic are the second component of the current antibiotic repository. One such example, the synthetic fluoroquinolones are a class of highly effective and broad spectrum antibiotics [ 236 ]. However, recent efforts based on high-throughput screens of novel targets identified by bacterial genomics to discover and develop new synthetic scaffolds have not yet been as successful as natural products [ 237 , 238 ].…”

Section: Newer Agents For CDImentioning

confidence: 99%

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Tsutsumi¹,

Owusu²,

Hurdle³

et al. 2013

CTMC

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Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

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Section: Newer Agents For CDImentioning

confidence: 99%

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Tsutsumi¹,

Owusu²,

Hurdle³

et al. 2013

CTMC

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“…CACO-2 P app A-B (efflux ratio) 16. 7 (1.5) 0.44 (18) CLint in Liver Microsomes (µL/min/mg, rat/human) aeruginosa compared to compounds with two (e.g., 10) despite equal or better activity against E. coli. Six-membered saturated rings (e.g., piperazine, compound 20) offered no improvement in antimicrobial activity despite the fact that this group is present in ciprofloxacin.…”

Section: Resultsmentioning

confidence: 99%

“…1 From these landmark studies emerged one of the most successful classes of antibacterial agents with nearly 30 analogs approved for clinical use, and more still in the pipeline at various pharmaceutical companies. [2][3][4][5][6][7][8] Quinolone antibiotics exert their activity by binding to and stabilizing DNA cleavage complexes formed by two essential bacterial enzymes: DNA gyrase and topoisomerase IV. This results in blockade of DNA replication.…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria

et al. 2020

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Since their discovery over five decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC Quinolone Resistance Determining Region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gramnegative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex, but does not form significant contacts with residues in the Quinolone Resistance Determining Region.

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“…As indicated in Table 1 and Table 2 , compounds 14c , 14e , 14g , 16b and 17a and 17b displayed broad-spectrum antibacterial activity against the tested Gram positive and Gram negative bacteria as compared with ciprofloxacin. Ciprofloxacin is a broad spectrum widely used antibacterial and is considered the most potent marketed fluoroquinolone against gram-negative bacteria [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

Abdel‐Aziz

Eldehna

Farès

et al. 2015

IJMS

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In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.

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Review of the Quinolone Family

Cited by 11 publications

References 198 publications

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria

Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

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