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Synthesis and evaluation of unsymmetrical heterocyclic thioureas as potent β-glucuronidase inhibitors

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Abstract

Thiourea analogs 1–20 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. The compounds 9 (0.86 ± 0.01 μM), 6 (1.24 ± 0.01 μM), 16 (1.64 ± 0.02 μM) and 15 (2.12 ± 0.02 μM) showed potent activity. Other analogs 1–5, 7, 8, 10, 11, 13, 17, 20 showed better activity than standard drug d-saccharic acid 1,4-lactone (47.34 ± 0.21 μM) ranging 4.36–34.4 μM. All synthetic compounds were characterized by different spectroscopic methods. This study has identified a new class of potent inhibitors β-glucuronidase.

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Acknowledgments

Authors would like to acknowledge The Ministry of Agriculture (MOA) Malaysia and Universiti Teknologi MARA under MOA Grant File No. 100-RMI/MOA 16/6/2 (1/2013) and Higher Education Commission (HEC) Pakistan, under National Research Program for Universities (Project No. 20-1910) for the financial support.

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Authors and Affiliations

  1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia

    Muhammad Taha & Nor Hadiani Ismail

  2. Faculty of Applied Science, UiTM, 40450, Shah Alam, Selangor, Malaysia

    Muhammad Taha & Nor Hadiani Ismail

  3. Institute of Advance Research Studies in Chemical Sciences, University of Sindh, Jamshoro, Pakistan

    Waqas Jamil & Syed Muhammad Kashif

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

    Khalid Mohammed Khan & Uzma Salar

  5. Department of Chemistry, Hazara University, Mansehra, Pakistan

    Fazal Rahim

  6. Department of Forensic Medicine and Toxiciology, Liaquat University of Medical and Health Sciences, Jamshoro, Hyderabad, Sindh, Pakistan

    Yawar Latif

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  1. Muhammad Taha
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  2. Nor Hadiani Ismail
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  3. Waqas Jamil
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  4. Khalid Mohammed Khan
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  5. Uzma Salar
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  6. Syed Muhammad Kashif
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  7. Fazal Rahim
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Correspondence to Muhammad Taha.

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Taha, M., Ismail, N.H., Jamil, W. et al. Synthesis and evaluation of unsymmetrical heterocyclic thioureas as potent β-glucuronidase inhibitors. Med Chem Res 24, 3166–3173 (2015). https://doi.org/10.1007/s00044-015-1369-x

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  • DOI: https://doi.org/10.1007/s00044-015-1369-x

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