Elucidating the antimycobacterial mechanism of action of ciprofloxacin using metabolomics

Knoll, Kirsten Elke; Lindeque, Jeremie Zander; Adetomiwa, Adeniji Ayodele; Oosthuizen, Carel B.; Lall, Namrita; Loots, Du Toit

doi:10.20944/preprints202104.0443.v1

Cited by 5 publications

(1 citation statement)

References 132 publications

(162 reference statements)

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“…It has also been demonstrated that ciprofloxacin, in addition to its effect on DNA gyrase, can cause reduction in the amount of DNA, RNA, and protein, as well as phospholipids, galactose, arabinose, glucosamine, and the mycolic acid of the M. smegmatis cell wall. However, these findings should be confirmed in the further studies ( Figure 2 ) ( 11 ). Ciprofloxacin affects several Gram-positive bacteria such as Staphylococcus, Streptococcus, Enterococcus, Bacillus spp., and Mycobacterium .…”

Section: Ciprofloxacin Characteristicsmentioning

confidence: 66%

The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic

Shariati

Arshadi

Khosrojerdi

et al. 2022

Front. Public Health

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For around three decades, the fluoroquinolone (FQ) antibiotic ciprofloxacin has been used to treat a range of diseases, including chronic otorrhea, endocarditis, lower respiratory tract, gastrointestinal, skin and soft tissue, and urinary tract infections. Ciprofloxacin's main mode of action is to stop DNA replication by blocking the A subunit of DNA gyrase and having an extra impact on the substances in cell walls. Available in intravenous and oral formulations, ciprofloxacin reaches therapeutic concentrations in the majority of tissues and bodily fluids with a low possibility for side effects. Despite the outstanding qualities of this antibiotic, Salmonella typhi, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa have all shown an increase in ciprofloxacin resistance over time. The rise of infections that are resistant to ciprofloxacin shows that new pharmacological synergisms and derivatives are required. To this end, ciprofloxacin may be more effective against the biofilm community of microorganisms and multi-drug resistant isolates when combined with a variety of antibacterial agents, such as antibiotics from various classes, nanoparticles, natural products, bacteriophages, and photodynamic therapy. This review focuses on the resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing its efficacy.

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Section: Ciprofloxacin Characteristicsmentioning

confidence: 66%

The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic

Shariati

Arshadi

Khosrojerdi

et al. 2022

Front. Public Health

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Elucidating the Antimycobacterial Mechanism of Action of Decoquinate Derivative RMB041 Using Metabolomics

et al. 2021

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), still remains one of the leading causes of death from a single infectious agent worldwide. The high prevalence of this disease is mostly ascribed to the rapid development of drug resistance to the current anti-TB drugs, exacerbated by lack of patient adherence due to drug toxicity. The aforementioned highlights the urgent need for new anti-TB compounds with different antimycobacterial mechanisms of action to those currently being used. An N-alkyl quinolone; decoquinate derivative RMB041, has recently shown promising antimicrobial activity against Mtb, while also exhibiting low cytotoxicity and excellent pharmacokinetic characteristics. Its exact mechanism of action, however, is still unknown. Considering this, we used GCxGC-TOFMS and well described metabolomic approaches to analyze and compare the metabolic alterations of Mtb treated with decoquinate derivative RMB041 by comparison to non-treated Mtb controls. The most significantly altered pathways in Mtb treated with this drug include fatty acid metabolism, amino acid metabolism, glycerol metabolism, and the urea cycle. These changes support previous findings suggesting this drug acts primarily on the cell wall and secondarily on the DNA metabolism of Mtb. Additionally, we identified metabolic changes suggesting inhibition of protein synthesis and a state of dormancy.

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Advancements in Synthetic Strategies and Biological Effects of Ciprofloxacin Derivatives: A Review

Khwaza,

Mlala,

Aderibigbe

2024

IJMS

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Ciprofloxacin is a widely used antibiotic in the fluoroquinolone class. It is widely acknowledged by various researchers worldwide, and it has been documented to have a broad range of other pharmacological activities, such as anticancer, antiviral, antimalarial activities, etc. Researchers have been exploring the synthesis of ciprofloxacin derivatives with enhanced biological activities or tailored capability to target specific pathogens. The various biological activities of some of the most potent and promising ciprofloxacin derivatives, as well as the synthetic strategies used to develop them, are thoroughly reviewed in this paper. Modification of ciprofloxacin via 4-oxo-3-carboxylic acid resulted in derivatives with reduced efficacy against bacterial strains. Hybrid molecules containing ciprofloxacin scaffolds displayed promising biological effects. The current review paper provides reported findings on the development of novel ciprofloxacin-based molecules with enhanced potency and intended therapeutic activities which will be of great interest to medicinal chemists.

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Elucidating the antimycobacterial mechanism of action of ciprofloxacin using metabolomics

Cited by 5 publications

References 132 publications

The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic

The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic

Elucidating the Antimycobacterial Mechanism of Action of Decoquinate Derivative RMB041 Using Metabolomics

Advancements in Synthetic Strategies and Biological Effects of Ciprofloxacin Derivatives: A Review

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