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Novel fluoroquinolones analogues bearing 4-(arylcarbamoyl)benzyl: design, synthesis, and antibacterial evaluation

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Abstract

Bacterial resistance to fluoroquinolone has been increasing at an alarming rate worldwide. In an attempt to find more potent anti-bacterial agents, an efficient, straightforward protocol was performed to obtain a large substrate scope of novel ciprofloxacin and sarafloxacin analogues conjugated with 4-(arylcarbamoyl)benzyl 7a–ab. All prepared compounds were evaluated for their anti-bacterial activities against three gram-positive strains (Methicillin resistant staphylococcus aureus (MRSA), Staphylococcus aureus, and Enterococcus faecalis) as well as three gram-negative strains (Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli) through three standard methods including broth microdilution, agar-disc diffusion, and agar-well diffusion assays. Most of the compounds exhibited great to excellent anti-bacterial potencies against MRSA and S. aureus. Among the targeted compounds, derivative 7n exhibited great antibacterial potency, which was noticeably more potent than parent ciprofloxacin. Subsequently, a molecular docking study was performed for this compound to find out its probable binding mode with the active site of S. aureus DNA gyrase (PDB ID: 2XCT).

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Funding

This work was supported and funded by Tehran University of Medical Sciences (TUMS); Grant Nos. 9211266096 and 9123120022.

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Authors and Affiliations

  1. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Fariba Peytam & Alireza Foroumadi

  2. Faculty of Medicine, Eastern Mediterranean University, via Mersin 10, Famagusta, Northern Cyprus, Turkey

    Maryam Norouzbahari, Gizem Şanlıtürk & Mümtaz Güran

  3. Final International University, Kyrenia via Mersin 10, TRNC, Catalkoy, Turkey

    Maryam Norouzbahari

  4. International Campus-School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Toktam Saadattalab

  5. Department of Chemistry, Faculty of Medicine, Eastern Mediterranean University, via Mersin 10, Famagusta, Northern Cyprus, Turkey

    Gizem Şanlıtürk

  6. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Loghman Firoozpour, Zahra Emamgholipour, Mahtab Ghasemi Dogaheh, Mohammad Nikou, Maliheh Barazandeh Tehrani & Alireza Foroumadi

  7. Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran, Iran

    Hamid Reza Bijanzadeh

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  1. Fariba Peytam
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  2. Maryam Norouzbahari
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Contributions

Prof. AF designed the study and conducted the experiments. Dr. FP, TS, and MN synthesized the targeted compounds. Dr. FP, Dr. MGD, and Dr. HRB wrote the manuscript and analyzed the characterization data. Dr. LF and Dr. ZE carried out the docking studies. Dr. MN, Dr. MG, and GŞ performed the biological evaluations. Dr. MBT revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Maryam Norouzbahari or Alireza Foroumadi.

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Peytam, F., Norouzbahari, M., Saadattalab, T. et al. Novel fluoroquinolones analogues bearing 4-(arylcarbamoyl)benzyl: design, synthesis, and antibacterial evaluation. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10676-w

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