Cheng Yang,Pei-Zhi Dong,Zhou-Ning Jiang,Yanan Li,Yue-Hong Pang
The illegal addition of phosphodiesterase-5 (PDE-5) inhibitors in functional food poses significant food safety risks and health issues, requiring a sensitive and effective enrichment and detection method. Herein, a magnetic COFs (Fe 3 O 4 @TpDBA) was prepared by a layer-by-layer growth strategy. TpDBA was synthesized through the condensation of 1,3,5- Triformylphloroglucinol (Tp) and 4,4′-diamino-(1,1′-biphenyl)-3,3′-dicarboxylic acid (DBA). Fe 3 O 4 @TpDBA was used as an adsorbent for magnetic solid-phase extraction (MSPE) of PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil), which enabled their efficient enrichment within 2 min. The lower binding energy value obtained through molecular docking calculations indicates stronger binding ability. The prepared Fe 3 O 4 @TpDBA exhibited high chemical stability (resistant to acid, alkali and organic reagents) and good reusability (10 adsorption/desorption cycles). Coupled with high-performance liquid chromatography-tandem mass spectrometry, Fe 3 O 4 @TpDBA-MSPE exhibited great potential in PDE-5 inhibitors. The developed method was optimized and validated, exhibiting a wide linear range and low limits of detection. Moreover, it was successfully applied to the determination of three PDE-5 inhibitors in five functional foods.
Multidrug resistance (MDR) is a significant challenge in cancer treatment, with limited effective strategies available. Neuropilin-1 (NRP1) is emerging as a potential therapeutic target for overcoming drug resistance, but its role in MDR and the identification of potential inhibitors require further exploration. In this study, we investigated the role of NRP1 in MDR and identifies potential inhibitors targeting NRP1. Elevated NRP1 expression was observed in oxaliplatin (OXP)-resistant HCT116 (HCT116/L) and cisplatin (DDP)-resistant A549 cells (A549/DDP). Virtual screening and biological assays identified pitavastatin (Ptv) as a potent NRP1 inhibitor that restored chemosensitivity in resistant cells both in vitro and in vivo . Mechanistic studies revealed that Ptv directly binds to NRP1, promotes degradation of Zinc finger X-chromosomal protein (ZFX), and disrupts the NRP1-ZFX axis to reverse MDR. This study provides promising prospects for targeting the NRP1-ZFX axis as a therapeutic strategy for MDR and highlights the potential clinical application of Ptv in diseases involving NRP1.
危险品化学品经营许可证（带存储）