Rapid colorimetric assay-guided discovery of α-glucosidase inhibitors from natural products using a MOF-818@Pt nanozyme.
α-Glucosidase (α-Glu) inhibitors are important therapeutic agents for the treatment of type 2 diabetes mellitus. However, the rapid discovery of such bioactive compounds from natural products remains challenging.
In this study, a MOF-818@Pt nanozyme-based colorimetric screening strategy was developed for the efficient discovery of α-Glu inhibitors from natural sources. The MOF-818@Pt composite, synthesized via an in-situ reduction-deposition method, exhibited excellent peroxidase-like activity and was thoroughly characterized. Using α-arbutin as the substrate, the proposed nanozyme-based system enabled sensitive detection of α-Glu activity, exhibiting a good linear relationship within the concentration range of 0.05-120 U/L (R2 = 0.991), along with strong anti-interference ability, satisfactory reproducibility, and long-term stability. This method was successfully applied to the bioactivity-guided fractionation of Myrciaria cauliflora, leading to the enrichment of ten subfractions (GH1-GH10) with significant α-Glu inhibitory activity. Feature-based molecular networking analysis revealed that these subfractions are predominantly composed of phloroglucinols, terpenoids, polyketides, and meroterpenoids. Molecular docking studies demonstrated that representative compounds from each class could bind within the active site of α-Glu, forming hydrogen bonds with key residues including Arg213, Asp215, Glu277, Gln279, and Asp352.
This work establishes a rapid, simple, and high-throughput strategy for screening α-Glu inhibitors from complex natural product matrices, providing a promising technological platform for natural product-based drug discovery.
In this study, a MOF-818@Pt nanozyme-based colorimetric screening strategy was developed for the efficient discovery of α-Glu inhibitors from natural sources. The MOF-818@Pt composite, synthesized via an in-situ reduction-deposition method, exhibited excellent peroxidase-like activity and was thoroughly characterized. Using α-arbutin as the substrate, the proposed nanozyme-based system enabled sensitive detection of α-Glu activity, exhibiting a good linear relationship within the concentration range of 0.05-120 U/L (R2 = 0.991), along with strong anti-interference ability, satisfactory reproducibility, and long-term stability. This method was successfully applied to the bioactivity-guided fractionation of Myrciaria cauliflora, leading to the enrichment of ten subfractions (GH1-GH10) with significant α-Glu inhibitory activity. Feature-based molecular networking analysis revealed that these subfractions are predominantly composed of phloroglucinols, terpenoids, polyketides, and meroterpenoids. Molecular docking studies demonstrated that representative compounds from each class could bind within the active site of α-Glu, forming hydrogen bonds with key residues including Arg213, Asp215, Glu277, Gln279, and Asp352.
This work establishes a rapid, simple, and high-throughput strategy for screening α-Glu inhibitors from complex natural product matrices, providing a promising technological platform for natural product-based drug discovery.
Authors
Zhang Zhang, Chen Chen, Huang Huang, Mou Mou, Qin Qin, Yang Yang, Jiang Jiang, Huang Huang
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