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

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, -glucosidase and -amylase. As expected, the molecular hybrids exhibited significantly greater inhibitory activity against -glucosidase (IC50=2.259x10(-6)-1.160x10(-4)mol/L), relative to their simple rhodanine counterparts (IC50=3.056x10(-4)-9.494x10(-4)mol/L). Amongst the screened derivatives compounds 6a and 6f displayed a 3-fold and 42-fold greater potency against -glucosidase (IC50=2.854x10(-5) and 2.259x10(-6)mol/L, respectively) compared to the standard drug, acarbose. The designed molecular conjugates displayed an improved binding affinity toward -glucosidase than -amylase. Compound 6d was identified as the most potent inhibitor of -amylase (IC50=6.377x10(-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 -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.