Cerium-Based Metal–Organic Framework Nanocrystals for Colorimetric Screening of α-Glucosidase Inhibitors

The screening method for α-glucosidase (α-Glu) inhibitors plays a crucial role in the development of antidiabetic drugs. This study introduces cerium-based metal–organic framework (Ce-MOF) nanocrystals for the highly sensitive colorimetric detection of α-Glu inhibitors. The synthesized Ce-MOF nanocrystals exhibited excellent oxidase-like activity, efficiently catalyzing the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to generate a blue product (oxTMB) with a strong absorption peak at 652 nm, enabling quantitative analysis using spectroscopic techniques. Notably, hydroquinone (HQ) can reduce the blue oxTMB to the colorless TMB. Specifically, α-Glu can hydrolyze α-arbutin to generate HQ, which subsequently reduces the oxidase activity of Ce-MOF. However, the addition of α-Glu inhibitors in the system limited the production of HQ, thereby maintaining the oxidase-like activity stability of Ce-MOF. Leveraging this mechanism, a screening method for α-Glu inhibitors was developed. This method overcomes the limitations of the conventional p-nitrophenyl-α-d-glucopyranoside (p-NPG) assay and effectively avoids potential interference from hydrogen peroxide introduced by peroxidase-like nanomaterials, significantly enhancing the detection sensitivity. The reliability and accuracy of this method were validated, demonstrating the highly sensitive determination of acarbose with an IC50 value of 7.04 μM and a detection limit of 3.2 nM. Moreover, this method has been successfully applied to screen potential α-Glu inhibitors from natural flavonoid compounds.