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New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro

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Abstract

Combating pathological conditions related to hyperactivity of enzymes remains a formidable challenge for health. Small molecules therapy constitutes one of the means to circumvent the medical disorders resulting from enzyme hyperactivity. In this regard, we have synthesized structurally diverse amino acid hybrid Schiff bases (5a–5l and 10a–10k) and evaluated them for carbonic anhydrase II, α-glucosidase, and urease inhibitory potential. These new chemical scaffolds showed variable efficacies against the selected enzymes. The results indicated that compounds 5b (11.8 ± 1.33 µM), 10i (83.3 ± 1.13 µM), and 10f (88.2 ± 2.27 µM) are the most active scaffolds against carbonic anhydrase II, α-glucosidase, and urease, respectively. A structure–activity relationship revealed the most structural features contributing to the overall activities. Molecular docking suggested that these compounds possess excellent binding interactions with the active site residues of the targets by interacting through hydrogen bonding, π–π, and π–cation interactions.

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Acknowledgements

The authors are grateful to The Research Council (TRC), Oman, for funding through the project (BFP/RGP/CBS/18/011) and University of Nizwa, Oman, for the generous support.

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Authors and Affiliations

  1. Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, PC 616, Nizwa, Sultanate of Oman

    Kashif Rafiq, Majid Khan, Ajmal Khan, Najeeb Ur Rehman, Balqees Essa Mohammad Al-Yahyaei, Mohammed Khiat, Sobia Ahsan Halim & Ahmed Al-Harrasi

  2. Department of Chemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan

    Kashif Rafiq & Niaz Muhammed

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

    Majid Khan

  4. Department of Chemistry, Bacha Khan University Charsadda, Charsadda, 24420, Khyber Pakhtunkhwa, Pakistan

    Zarbad Shah

  5. Department of Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany

    Rene Csuk

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  1. Kashif Rafiq
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Rafiq, K., Khan, M., Muhammed, N. et al. New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro. Med Chem Res 30, 712–728 (2021). https://doi.org/10.1007/s00044-020-02696-0

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