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

  • Parvesh Singh
  • Serisha Mothilal
  • Nagaraju Kerru
  • Ashona Singh-Pillay
  • Lalitha Gummidi
  • Ochuko L. Erukainure
  • Md. Shahidul Islam
Original Research
  • 32 Downloads

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.

Keywords

Pyrazole Rhodanine Molecular hybrids α-glucosidase α-amylase 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2272_MOESM1_ESM.doc (5 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Parvesh Singh
    • 1
  • Serisha Mothilal
    • 1
  • Nagaraju Kerru
    • 1
  • Ashona Singh-Pillay
    • 1
  • Lalitha Gummidi
    • 1
  • Ochuko L. Erukainure
    • 2
  • Md. Shahidul Islam
    • 2
  1. 1.School of Chemistry and PhysicsUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Biomedical Research Lab, Department of Biochemistry, School of Life SciencesUniversity of KwaZulu-NatalDurbanSouth Africa

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