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Synthesis, In Vitro α-Amylase Activity, and Molecular Docking Study of New Benzimidazole Derivatives

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Abstract

New benzimidazole derivatives were synthesized by reacting substituted phenacyl bromides with 1H-benzimidazole-2-thiols. The synthesized compounds were characterized through 1H and 13C NMR and high-resolution mass spectra. Their evaluation for α-amylase activity revealed inhibitory potential with IC50 values ranging from 1.20±0.05 to 19.10±0.30 μM against IC50 = 1.70±0.10 μM for the standard drug acarbose. Among the examined series, 2-[(1H-benzimidazole-2-yl)sulfanyl]-1-(3–nitrophenyl)ethan-1-one (IC50 = 1.20±0.05 µM) was the most potent. Other nitro-substituted analogs showed good potency with IC50 values of 2.10±0.10, 2.20±0.10 and 2.10±0.10 µM. Limited structure–activity relationship was established for all derivatives based on the nature, position, and number of substituents on the aryl ring. Binding sites of the most active compounds were determined by the molecular docking study.

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Funding

The authors thank the Higher Education Commission of Pakistan for providing a research grant under National Research Program for Universities (project nos. 5721, 5092).

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Authors and Affiliations

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

    Hayat Ullah

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

    Hafeez Ullah, F. Khan, F. Rahim & I. Uddin

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

    M. Taha

  4. Department of Zoology, Faculty of Life Science, The Women University, 66000, Multan, Punjab, Pakistan

    M. Sarfraz

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

    S. A. Ali Shah

  6. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia

    S. A. Ali Shah

  7. Institute of Biological Sciences, Sarhad University of Science and Information Technology, 25000, Peshawar, Pakistan

    A. Aziz

  8. Department of Chemistry, The Women University, 60000, Multan, Punjab, Pakistan

    S. Mubeen

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  1. Hayat Ullah
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Correspondence to Hayat Ullah or F. Rahim.

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Ullah, H., Ullah, H., Taha, M. et al. Synthesis, In Vitro α-Amylase Activity, and Molecular Docking Study of New Benzimidazole Derivatives. Russ J Org Chem 57, 968–975 (2021). https://doi.org/10.1134/S1070428021060130

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