Abstract
A novel series of N-methyl/benzyl-substituted benzimidazolyl-linked para-substituted benzyl-based compounds containing 2,4-thiazolidinediones, dimethyl malonate (DMM), and diethyl malonate (DEM) 17–27 were designed, docked, synthesized, and evaluated for their antidiabetic activity studies. Structures of all the synthesized compounds were confirmed through 1H NMR, 13C NMR, FTIR, and mass spectrometry. Four targeted compounds (17–18 and 22–23) showed good inhibitory potential in the range of 4.10 ± 0.01 to 9.12 ± 0.06 µM. Furthermore, synthesized compounds 17–27 were evaluated for their antioxidant potential and compared with standard ascorbic acid and results showed that compound 18 (EC50 = 0.176 ± 0.002 mM) being the most active. Compounds 17–18 and 22–23 exhibited prominent antidiabetic as well as antioxidant activity. Compound 18 was considered a promising candidate for this series. The designed molecules were docked into α-glucosidase protein (PDB Code. 3TOP) to develop a correlation with the α-glucosidase inhibition studies and were also additionally docked into PPARγ proteins (PDB ID: 2PRG) with rosiglitazone (standard drug) to study their PPARγ binding affinity in comparison with rosiglitazone and to classify these compounds for their PPARγ agonistic behavior.
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Acknowledgements
Authors are thankful to the Punjabi University, Patiala authorities for providing the necessary research facilities. We are also grateful to Director and Mr Avtar Singh of Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, Chandigarh, respectively, for extending the facilities for spectral analysis of the compounds reported in this paper. One of the authors, GS, is thankful to the Ministry of Social Justice and Empowerment, Govt of India for providing research fellowship.
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Singh, G., Singh, A., Singh, V. et al. Synthesis, molecular docking, α-glucosidase inhibition, and antioxidant activity studies of novel benzimidazole derivatives. Med Chem Res 29, 1846–1866 (2020). https://doi.org/10.1007/s00044-020-02605-5
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DOI: https://doi.org/10.1007/s00044-020-02605-5