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Synthesis, in vitro \(\alpha \)-glucosidase inhibitory activity, and in silico study of (E)-thiosemicarbazones and (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives

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Abstract

This study is focused on the identification of thiazole-based inhibitors for the \(\alpha \)-glucosidase enzyme. For that purpose, (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives were synthesized in two steps and characterized by various spectroscopic techniques. All derivatives and intermediates were evaluated for their in vitro \(\alpha \)-glucosidase inhibitory activity. Thiosemicarbazones 20 and 35, and cyclized thiazole derivatives 2, 5–11, 13, 15, 21–24, 27–31, and 36–37 showed significant inhibitory potential in the range of \(\hbox {IC}_{50}=6.2\pm 0.19\)–\(43.6\pm 0.23~\upmu \hbox {M}\) as compared to standard acarbose (\(\hbox {IC}_{50}=37.7\pm 0.19~\upmu \hbox {M}\)). A molecular modeling study was carried out to understand the binding interactions of compounds with the active site of enzyme.

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Acknowledgements

This work was supported by the Higher Education Commission (HEC) Pakistan under the National Research Program for Universities (Project No. 20-1910).

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Authors and Affiliations

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

    Muhammad Ali, Khalid Mohammed Khan, Uzma Salar, Basharat Ali, Shahbaz Shamim & Farman Ali

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

    Mohammed Ashraf & Sujhla Hamid

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

    Khalid Mohammed Khan & Muhammad Taha

  4. Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan

    Abdul Wadood & Muhammad Riaz

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

    Shahnaz Perveen

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  1. Muhammad Ali
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Ali, M., Khan, K.M., Salar, U. et al. Synthesis, in vitro \(\alpha \)-glucosidase inhibitory activity, and in silico study of (E)-thiosemicarbazones and (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives. Mol Divers 22, 841–861 (2018). https://doi.org/10.1007/s11030-018-9835-2

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