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Synthesis, molecular docking, and biological evaluation of nitroimidazole derivatives as potent urease inhibitors

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The objective of this study was to design new nitroimidazole-based derivatives as strong urease inhibitors for the treatment of H. pylori infections. New series of nitroimidazole derivatives, 4a–k, were synthesized by using TBTU as the catalyst and assayed as Jack bean urease inhibitors. The facile synthetic approach was employed for the preparation of targeted molecular designs in good to excellent yields, ranged from 65 to 92%. Accordingly, all the synthesized compounds, 4a–k (IC50 = 1.43–7.72 μM), were more potent than the standard urease inhibitors, thiourea, and hydroxyurea. Among the derivatives, 4d had the most urease inhibitor activity (IC50 = 1.43 μM), over 15-fold more potent than thiourea and 70-fold than hydroxyurea. True to form, the result of molecular docking studies was in good congruence with those obtained from in vitro tests.

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Acknowledgements

The research reported in this publication was supported by Elite Researcher Grant Committee under award number [996450] from the National Institute for Medical Research Development (NIMAD), Tehran, Iran.

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Authors and Affiliations

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

    Meysam Talebi, Elham Hamidian, Fatemeh Niasari-Naslaji, Sogand Rahmani, Faezeh Sadat Hosseini, Shahin Boumi, Mohammad Nazari Montazer, Mehdi Asadi & Massoud Amanlou

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Massoud Amanlou

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Talebi, M., Hamidian, E., Niasari-Naslaji, F. et al. Synthesis, molecular docking, and biological evaluation of nitroimidazole derivatives as potent urease inhibitors. Med Chem Res 30, 1220–1229 (2021). https://doi.org/10.1007/s00044-021-02727-4

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