Comparative α-glucosidase and α-amylase inhibition studies of rhodanine–pyrazole conjugates and their simple rhodanine analogues
- University of KwaZulu-Natal, School of Chemistry and Physics (South Africa)
- University of KwaZulu-Natal, Biomedical Research Lab, Department of Biochemistry, School of Life Sciences (South Africa)
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 (IC{sub 50} = 2.259 × 10{sup −6}–1.160 × 10{sup −4} mol/L), relative to their simple rhodanine counterparts (IC{sub 50} = 3.056 × 10{sup −4}–9.494 × 10{sup −4} mol/L). Amongst the screened derivatives compounds 6a and 6f displayed a 3-fold and 42-fold greater potency against α-glucosidase (IC{sub 50} = 2.854 × 10{sup −5} and 2.259 × 10{sup −6}mol/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 (IC{sub 50} = 6.377 × 10{sup −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 (OCH{sub 3}) 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.
- OSTI ID:
- 22936214
- Journal Information:
- Medicinal Chemistry Research (Print), Vol. 28, Issue 2; Other Information: Copyright (c) 2019 Springer Science+Business Media, LLC, part of Springer Nature; Country of input: International Atomic Energy Agency (IAEA); ISSN 1054-2523
- Country of Publication:
- United States
- Language:
- English
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