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Trisubstituted Imidazole and N-Propargyl Imidazole Analogues: Synthesis, Characterization, In Silico Studies and Enzyme Inhibitory Properties

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Abstract

In recent years, the α-amylase, pancreatic lipase (PL), and β-glucuronidase enzymes have received much attention as they promise to be potential drug targets for obesity and diabetes-related diseases. In this study, the synthesis and characterization of newly designed tricyclic imidazopyrrolopyrazine analogues with the potential to affect these enzymes were evaluated. The pharmacological evaluation of all imidazopyrrolopyrazine analogues revealed that all the synthesized analogues displayed excellent inhibitory effects against α-amylase, with the IC50 values of these analogues ranging from 4.05±0.7 to 5.61±0.8 µM. The IC50 values of all synthesized analogues were also found to be effective inhibitors, ranging from 5.2±0.5 to 13.7±2.3 µM, against pancreatic lipase. Furthermore, all analogues exhibited moderate inhibition in a wide range of 151.4±9.1 to 302.5±7.9 µM against β-glucuronidase. Additionally, all the synthesized analogues displayed moderate binding affinity with Ferric Reducing Antioxidant Power (FRAP), and low binding affinity with Oxygen Radical Absorbance Capacity (ORAC). This study provides valuable potential for the new tricyclic imidazopyrrolopyrazine analogues in further pharmacological studies.

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Fig. 1.

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ACKNOWLEDGMENTS

The authors express their gratitude to the Faculty of Pharmacy at Van Yuzuncu Yil University for providing the necessary facilities to carry out this research. The Van Yuzuncu Yil University Scientific Research Projects Chairmanship (BAP) is acknowledged for their support of this work (project no. TYL-2018-6913).

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, 65250, Van, Turkey

    M. S. Altiok, B. Kuzu & I. Bildirici

  2. Department of Chemistry, Faculty of Education, Van Yuzuncu Yil University, 65250, Van, Turkey

    A. Cetin

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  1. M. S. Altiok
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Correspondence to I. Bildirici.

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Altiok, M.S., Cetin, A., Kuzu, B. et al. Trisubstituted Imidazole and N-Propargyl Imidazole Analogues: Synthesis, Characterization, In Silico Studies and Enzyme Inhibitory Properties. Russ J Gen Chem 93, 666–679 (2023). https://doi.org/10.1134/S1070363223030210

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