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Comparative α-glucosidase and α-amylase inhibition studies of rhodanine–pyrazole conjugates and their simple rhodanine analogues

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Abstract

Novel rhodanine–pyrazole conjugates (6a–i) and their simple rhodanine analogues (8a–e) were prepared and comparatively screened for their antidiabetic activities against enzymatic targets, α-glucosidase and α-amylase. As expected, the molecular hybrids exhibited significantly greater inhibitory activity against α-glucosidase (IC50 = 2.259 × 10−6–1.160 × 10−4 mol/L), relative to their simple rhodanine counterparts (IC50 = 3.056 × 10−4–9.494 × 10−4 mol/L). Amongst the screened derivatives compounds 6a and 6f displayed a 3-fold and 42-fold greater potency against α-glucosidase (IC50 = 2.854 × 10−5 and 2.259 × 10−6mol/L, respectively) compared to the standard drug, acarbose. The designed molecular conjugates displayed an improved binding affinity toward α-glucosidase than α-amylase. Compound 6d was identified as the most potent inhibitor of α-amylase (IC50 = 6.377 × 10−5 mol/L) with a 1.5-fold greater inhibitory activity than acarbose. Structural assessment of the molecules revealed that electron withdrawing (Cl) and electron donating (OCH3) groups at the ortho-position played a significant role in the inhibitory activity. Molecular docking studies of the molecular conjugates and simple rhodanine analogues in the active site of α-glucosidase were performed to describe and highlight the putative binding interactions attributing to the selective inhibition. The identification of these novel rhodanine–pyrazole molecular hybrids forms part of a potential treatment in the management of diabetes.

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Acknowledgements

The authors would like to acknowledge the support from the NRF South Africa (Grant UID: 99563) as well as the CHPC in Cape Town for access to computational resources.

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Authors and Affiliations

  1. School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, 4000, South Africa

    Parvesh Singh, Serisha Mothilal, Nagaraju Kerru, Ashona Singh-Pillay & Lalitha Gummidi

  2. Biomedical Research Lab, Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa

    Ochuko L. Erukainure & Md. Shahidul Islam

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  1. Parvesh Singh
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Correspondence to Parvesh Singh.

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Singh, P., Mothilal, S., Kerru, N. et al. Comparative α-glucosidase and α-amylase inhibition studies of rhodanine–pyrazole conjugates and their simple rhodanine analogues. Med Chem Res 28, 143–159 (2019). https://doi.org/10.1007/s00044-018-2272-z

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