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Syntheses, in vitro evaluation and molecular docking studies of 5-bromo-2-aryl benzimidazoles as α-glucosidase inhibitors

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Abstract

Based on the previous reports on α-glucosidase inhibitory activity of benzimidazole class, we intend to evaluate further this class as potential inhibitors of α-glucosidase enzyme. Thus, in the current study synthesis of 5-bromo-2-aryl benzimidazole derivatives 1–25 was carried out. All the synthetic compounds were characterized by different spectroscopic techniques EIMS, HRMS, 1H-NMR, and 13C-NMR. Molecular docking was also performed on the selected compounds 1, 4, 7, and 17 having varying substitution pattern in order to understand the molecular interaction of molecules with the active site of the enzyme. All compounds were evaluated for their in vitro α-glucosidase inhibitory activities. Twenty-three compounds out of twenty-five showed excellent to moderate activity in the range of IC50 = 12.4–103.2 μM. Inhibitory results were compared with the standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 1 (IC50 = 37.82 ± 0.08 μM), 9 (IC50 = 37.76 ± 0.05 μM), 12 (IC50 = 24.96 ± 0.09 μM), 16 (IC50 = 21.15 ± 0.08 μM) and 17 (IC50 = 8.34 ± 0.02 μM) showed excellent inhibition as compared to standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Especially, 17 (IC50 = 8.34 ± 0.02 μM) was found to be five-fold more active than the standard.

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Acknowledgments

The authors are thankful to the Higher Education Commission (HEC) Pakistan, for their financial support to Research Project No. 20-2073 under National Research Program for Universities.

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Authors and Affiliations

  1. Jinnah University for Women, 5-C, Nazimabad, Karachi, 74600, Pakistan

    Tanzila Arshad & Najma Rasool

  2. 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 & Shafqat Hussain

  3. Deparment of Chemistry, Karakoram International University, Gilgit, Pakistan

    Shafqat Hussain

  4. Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    Tehreem Tahir & Mohammed Ashraf

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

    Abdul Wadood & Muhammad Riaz

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

    Shahnaz Perveen

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

    Muhammad Taha & Nor Hadiani Ismail

  8. Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam, 40450, Selangor D. E., Malaysia

    Muhammad Taha & Nor Hadiani Ismail

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  1. Tanzila Arshad
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  2. Khalid Mohammed Khan
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  3. Najma Rasool
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  4. Uzma Salar
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  5. Shafqat Hussain
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  6. Tehreem Tahir
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  7. Mohammed Ashraf
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  8. Abdul Wadood
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  9. Muhammad Riaz
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  10. Shahnaz Perveen
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  11. Muhammad Taha
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Correspondence to Khalid Mohammed Khan.

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Arshad, T., Khan, K.M., Rasool, N. et al. Syntheses, in vitro evaluation and molecular docking studies of 5-bromo-2-aryl benzimidazoles as α-glucosidase inhibitors. Med Chem Res 25, 2058–2069 (2016). https://doi.org/10.1007/s00044-016-1614-y

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