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Synthesis, β-Glucuronidase Inhibitory Activity, and Molecular Docking Study of Oxazole Derivatives

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Abstract

A series of 4-aryl-2-[2-(arylmethylidene)hydrazinyl]-1,3-oxazoles were synthesized from the corre­sponding aromatic aldehyde semicarbazones and phenacyl bromides. The synthesized compounds were characterized by NMR and high-resolution mass spectra and evaluated for their inhibitory activity against β-glucuronidase. All compounds showed a varying degree of inhibitory potential (IC50) ranging from 2.40±0.10 to 43.20±0.20 µM in comparison with the standard drug D-saccharic acid 1,4-lactone (IC50 = 48.4±1.25 µM). The most potent analogs displayed IC50 values of 2.40±0.10 and 5.30±0.20 µM. A limited structure–activity relationship analysis was performed, which showed that the nature, position, and number of the substituents on phenyl ring are the major factors responsible for the inhibitory activity. A molecular docking study was carried out to determine the binding interaction of the most potent compounds in the active site of the enzyme.

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Authors and Affiliations

  1. Department of Chemistry, University of Okara, 56300, Okara, Punjab, Pakistan

    H. Ullah, Z. Gul & S. Ullah

  2. Department of Chemistry, Hazara University, 21300, Mansehra, Khyber Pakhtunkhwa, Pakistan

    H. Zada, S. Hayat, F. Khan & F. Rahim

  3. Department of Zoology, Wildlife and Fisheries, University of Agriculture, 38000, Faisalabad, Pakistan

    M. Sarfraz

  4. Department of Biochemistry, University of Okara, 56300, Okara, Punjab, Pakistan

    M. Ullah

  5. Center for Nanoscience, University of Okara, 56300, Okara, Punjab, Pakistan

    M. U. Khan

  6. Department of Biochemistry, Abdul Wali Khan University Mardan, 23200, Mardan, Pakistan

    A. Wadood & A. Rehman

  7. Department of Molecular Biology and Biochemistry, University of California, 92697-3900, Irvine, CA, USA

    A. Rehman

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  1. H. Ullah
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Ullah, H., Zada, H., Hayat, S. et al. Synthesis, β-Glucuronidase Inhibitory Activity, and Molecular Docking Study of Oxazole Derivatives. Russ J Org Chem 59, 174–180 (2023). https://doi.org/10.1134/S1070428023010190

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  • DOI: https://doi.org/10.1134/S1070428023010190

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