Oxindole-pyrrole-piperazine hybrids as novel α-glucosidase inhibitors: Design, synthesis and evaluation

α-Glucosidase acts as one therapeutic target for diabetes. For finding novel α-glucosidase inhibitors, oxindole-pyrrole-piperazine hybrids ( OPP-1∼24 ) were synthesized. Inhibition evaluation revealed that all hybrids ( OPP-1∼X24 ) demonstrated potent α-glucosidase inhibitory activity with IC ₅₀ values of 6.34 ∼ 27.95 μM, obviously better than that of acarbose. Among them, OPP-11 , as the strongest inhibitor (IC ₅₀ = 6.34 μM), acted as a mixed-type inhibitor. Fluorescence quenching experiments indicated interaction of OPP-11 with α-glucosidase following a static quenching mechanism. Circular dichroism and 3D fluorescence results revealed OPP-11 binding induced α-glucosidase conformation changes. Molecular docking simulations further elucidated the detailed binding mode of OPP-11 on α-glucosidase. Collectively, the oxindole-pyrrole-piperazine scaffold represents a promising template to find α-glucosidase inhibitors.