<p>Developing efficient, low-cost, and portable screening methods for <i>α</i>-glucosidase inhibitors (AGIs) is of great significance for discovering natural antidiabetic drugs. Accordingly, this study constructed a colorimetric dual-platform system utilizing Fe-doped MoO<sub>x</sub> (Fe-MoO<sub>v</sub>) nanozymes with superior peroxidase-like activity, featuring both high-throughput capability and portability. This system functions by linking <i>α</i>-glucosidase (<i>α</i>-Glu) activity to a colorimetric readout: active <i>α</i>-Glu leads to a colorless output, whereas its inhibition by an AGI preserves an intense blue color, allowing for straightforward visual identification. This mode gave rise to two platforms: the high-throughput screening (HTS) platform facilitated parallel analysis of 96–384 samples using a microplate reader for large-scale library screening, while the portable screening (PTS) platform provided rapid on-site assessment by delivering readable results within 46&#xa0;min via a smartphone. Experimentally, the system was validated using acarbose as a model AGI, achieving detection limits as low as 0.00411 µM for the HTS platform and 0.092 µM for the PTS one, along with robust interference tolerance. Furthermore, the sensing system was successfully applied to screen seven pentacyclic triterpenoids as potential AGIs. All compounds were confirmed as active inhibitors with IC<sub>50</sub> values clustering in the range 30–110 µM. Ursolic acid, the most potent inhibitor (IC<sub>50</sub> = 30.23 µM), exhibited 3.5-fold greater potency than the least active one. Molecular docking further elucidated their interaction mechanisms with <i>α</i>-Glu. In summary, this study presents an innovative screening strategy that is efficient, low-cost, and user-friendly, offering a new approach for the development of natural antidiabetic drugs.</p> Graphical Abstract <p></p>

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Advancing drug discovery: a colorimetric dual-platform system based on Fe-MoOv peroxidase mimetics for screening α-glucosidase inhibitors

  • Xuhui Tan,
  • Siqi Zeng,
  • Yao Nie,
  • Jiaren Song,
  • Wanchao Zuo,
  • Qing Yang,
  • Yingchao Fan,
  • Sha Liu,
  • Xiaofei Liu,
  • Jianjun Dai,
  • Yanmin Ju

摘要

Developing efficient, low-cost, and portable screening methods for α-glucosidase inhibitors (AGIs) is of great significance for discovering natural antidiabetic drugs. Accordingly, this study constructed a colorimetric dual-platform system utilizing Fe-doped MoOx (Fe-MoOv) nanozymes with superior peroxidase-like activity, featuring both high-throughput capability and portability. This system functions by linking α-glucosidase (α-Glu) activity to a colorimetric readout: active α-Glu leads to a colorless output, whereas its inhibition by an AGI preserves an intense blue color, allowing for straightforward visual identification. This mode gave rise to two platforms: the high-throughput screening (HTS) platform facilitated parallel analysis of 96–384 samples using a microplate reader for large-scale library screening, while the portable screening (PTS) platform provided rapid on-site assessment by delivering readable results within 46 min via a smartphone. Experimentally, the system was validated using acarbose as a model AGI, achieving detection limits as low as 0.00411 µM for the HTS platform and 0.092 µM for the PTS one, along with robust interference tolerance. Furthermore, the sensing system was successfully applied to screen seven pentacyclic triterpenoids as potential AGIs. All compounds were confirmed as active inhibitors with IC50 values clustering in the range 30–110 µM. Ursolic acid, the most potent inhibitor (IC50 = 30.23 µM), exhibited 3.5-fold greater potency than the least active one. Molecular docking further elucidated their interaction mechanisms with α-Glu. In summary, this study presents an innovative screening strategy that is efficient, low-cost, and user-friendly, offering a new approach for the development of natural antidiabetic drugs.

Graphical Abstract