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Design and synthesis of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids as new anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic and docking studies

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Abstract

Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a–n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a–n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4–231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC50 = 750.0 μM). Among them, 4,5-diphenyl-imidazol-1,2,3-triazoles possessing 2-chloro and 2-bromo-benzyl moieties (compounds 8g and 8i) demonstrated the most potent inhibitory activities toward α-glucosidase. The kinetic study of the compound 8g revealed that this compound inhibited α-glucosidase in a competitive mode. Furthermore, docking calculations of these compounds were performed to predict the interaction mode of the synthesized compounds in the active site of α-glucosidase.

Graphic abstract

A novel series of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a–n was synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1Himidazole and various benzyl azides. The synthesized compounds 8a–n were evaluated against yeast α-glucosidase and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC50 = 750.0 μM).

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Acknowledgements

This project was financially supported by the National Institute for Medical Research Development (NIMAD) (the Grant Number: 977073).

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Author notes

  1. Mohammad Sadegh Asgari and Maryam Mohammadi-Khanaposhtani contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran

    Mohammad Sadegh Asgari & Parviz Ranjbar Rashidi

  2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Maryam Mohammadi-Khanaposhtani

  3. Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran

    Zeinab Sharafi

  4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Faramarzi

  5. Food and Drug Research Institute, Food and Drug Administration, MOHE, Tehran, Iran

    Hossein Rastegar

  6. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, University of Medical Sciences, Tehran, Iran

    Ensieh Nasli Esfahani & Fatemeh Bandarian

  7. Department of Chemistry, Iran University of Science and Technology, Tehran, Iran

    Rahmatollah Rahimi

  8. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mahmood Biglar, Mohammad Mahdavi & Bagher Larijani

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Asgari, M.S., Mohammadi-Khanaposhtani, M., Sharafi, Z. et al. Design and synthesis of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids as new anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic and docking studies. Mol Divers 25, 877–888 (2021). https://doi.org/10.1007/s11030-020-10072-8

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