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Synthesis, molecular docking, antimicrobial evaluation, and DNA cleavage assay of new thiadiazole/oxadiazole ciprofloxacin derivatives

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Abstract

Herein we report the synthesis of new N-4-piperazinyl thiadiazole and oxadiazole ciprofloxacin derivatives and their antibacterial and antimycobacterial activities. Although thiadiazole ciprofloxacin derivatives compound showed broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative organisms, the oxadiazole derivatives exhibited weaker antibacterial and antimycobacterial activities than thiadiazole derivatives against most of the tested strains compared with the reference ciprofloxacin. Moreover, the antimycobacterial screening revealed that compounds which containing thiadiazole scaffold potently inhibited Mycobacterium smegmatis at MIC of 1.56 and 3.13, respectively, and modestly inhibited the drug-resistant strains. DNA cleavage assay revealed that thiadiazole ciprofloxacin derivatives inhibited supercoil relaxation, albeit to a lesser extent than ciprofloxacin, and it also increased the amount of nicked substrate produced.

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Acknowledgements

Our grateful thanks to Dr. Rehab M. Abd El-Baky for carrying out the antibacterial investigation at Department of Microbiology & Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt. Also, Dr. Safwat M Rabea, is greatly acknowledged for measuring NMR data of the synthesized compounds at British Colombia University, Canada.

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Correspondence to El-Shimaa M. N. Abdelhafez.

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Mohammed, H.H.H., Abbas, S.H., Abdelhafez, ES.M.N. et al. Synthesis, molecular docking, antimicrobial evaluation, and DNA cleavage assay of new thiadiazole/oxadiazole ciprofloxacin derivatives. Monatsh Chem 150, 1809–1824 (2019). https://doi.org/10.1007/s00706-019-02478-4

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