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Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors

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Abstract

Diabetes mellitus is a main global health apprehension. Macrovascular illnesses, neuropathy, retinopathy, and nephropathy are considered some of its severe hitches. Gliptins are a group of hypoglycemic agents that inhibit dipeptidyl peptidase-IV (DPP-IV) enzyme and support blood glucose-lowering effect of incretins. In the current research, synthesis, characterization, docking, and biological evaluation of fourteen Schiff’s bases 5a–f and 9a–h were carried out. Compound 9f revealed the best in vitro anti-DPP-IV activity of 35.7% inhibition at a concentration of 100 μM. Compounds 9c and 9f with the highest in vitro DPP-IV inhibition were subjected to the in vivo glucose-lowering test using vildagliptin as a positive inhibitor. Vildagliptin, 9c, and 9f showed significant reduction in the blood glucose levels of the treated mice after 30 min of glucose administration. Moreover, induced fit docking showed that these derivatives accommodated the enzyme binding site with comparable docking scores. Schiff’s bases can serve as promising lead for the development of new DPP-IV inhibitors.

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Acknowledgements

Authors acknowledge the support from the Deanship of Scientific Research at Al-Zaytoonah University of Jordan.

Funding

This work was funded by the Deanship of Scientific Research at Al-Zaytoonah University of Jordan (Grant number: 20/23/2019-2020).

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

    Reema Abu Khalaf, Maha Awad, Luay Al-Essa, Sara Mefleh, Dima Sabbah, Eveen Al-Shalabi & Ihsan Shabeeb

Authors
  1. Reema Abu Khalaf
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  2. Maha Awad
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  3. Luay Al-Essa
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  4. Sara Mefleh
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  5. Dima Sabbah
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  6. Eveen Al-Shalabi
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  7. Ihsan Shabeeb
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Contributions

Reema Abu Khalaf and Dima Sabbah designed and synthesized the targeted molecules. Luay Al-Essa, Maha Awad and Sara Mefleh made the biological evaluations. Eveen Al-Shalabi and Ihsan Shabeeb characterized the compounds.

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Correspondence to Reema Abu Khalaf.

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Abu Khalaf, R., Awad, M., Al-Essa, L. et al. Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors. Mol Divers 26, 1213–1225 (2022). https://doi.org/10.1007/s11030-021-10253-z

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  • DOI: https://doi.org/10.1007/s11030-021-10253-z

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