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Aryl hydrazones linked thiazolyl coumarin hybrids as potential urease inhibitors

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Abstract

Aryl hydrazones bearing thiazolyl coumarin hybrids 1–32 were prepared by following 'one-pot' two-steps reaction scheme. Various arylaldehydes were reacted to thiosemicarbazide under acidic condition to form aryl thiosemicarbazone intermediates which in turn treated with 3-bromoacetyl coumarin under basic condition to afford thiazolyl coumarin hybrids 1–32. All hybrids were recognized by EI- and HREI-MS and 1H- and 13C-NMR spectroscopic techniques. Compounds 1–32 were screened for in vitro inhibitory activity against urease enzyme and displayed good to moderate inhibitory potential in the ranges of IC50 = 16.29 ± 1.1–256.30 ± 1.4 µM. Worth stating that compound 21 (IC50 = 16.29 ± 1.1 µM) was identified as more potent urease inhibitor than the standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Derivatives 19 (IC50 = 77.67 ± 1.5 µM) and 30 (IC50 = 71.21 ± 1.6 µM) were found to be moderately active. Structure–activity relationship revealed that -F, -Cl, -OH, and -OMe groups and their respective positions on aryl ring are playing important role in urease enzyme inhibition. Molecular docking studies identified important interaction between the ligand (active hybrids) and urease active site.

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Acknowledgements

The authors are thankful to the Pakistan Academy of Sciences for providing financial support to Project No. (5-9/PAS/440).

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Authors and Affiliations

  1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Uzma Salar, Bakhtawer Qureshi, Khalid Mohammed Khan & Fouzia Naz

  2. Pakistan Academy of Sciences, 3-Constitution Avenue G-5/2, Islamabad, Pakistan

    Khalid Mohammed Khan

  3. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Uzma Salar & Zaheer Ul‑Haq

  4. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia

    Khalid Mohammed Khan & Muhammad Taha

  5. Department of Biochemistry, Abdul Wali Khan University, Mardan, KP, Pakistan

    Muhammad Arif Lodhi & Farman Ali Khan

  6. PCSIR Laboratories Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi, 75280, Pakistan

    Shahnaz Perveen

  7. Department of Chemistry, University of Baltistan, Skardu, Gilgit-Baltistan, Pakistan

    Shafqat Hussain

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  1. Uzma Salar
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Correspondence to Uzma Salar or Khalid Mohammed Khan.

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Salar, U., Qureshi, B., Khan, K.M. et al. Aryl hydrazones linked thiazolyl coumarin hybrids as potential urease inhibitors. J IRAN CHEM SOC 19, 1221–1238 (2022). https://doi.org/10.1007/s13738-021-02377-8

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