1.Multiple rapid-responsive probes for hypochlorite detection based on dioxetane luminophore derivatives
Sun YINGAI ; Gao YUQI ; Tang CHUNCHAO ; Dong GAOPAN ; Zhao PEI ; Peng DUNQUAN ; Wang TIANTIAN ; Du LUPEI ; Li MINYONG
Journal of Pharmaceutical Analysis 2022;12(3):446-452
In recent years,various methods for detecting exogenous and endogenous hypochlorite have been studied,considering its essential role as a biomolecule.However,the existing technologies still pose obstacles such as their invasiveness,high costs,and complicated operation.In the current study,we developed a glow-type chemiluminescent probe,hypochlorite chemiluminescence probe(HCCL)-1,based on the scaffold of Schaap's 1,2-dioxetane luminophores.To better explore the physiological and pathological functions of hypochlorite,we modified the luminophore scaffold of HCCL-1 to develop several probes,including HCCL-2,HCCL-3,and HCCL-4,which amplify the response signal of hypo-chlorite.By comparing the luminescent intensities of the four probes using the IVIS? system,we determined that HCCL-2 with a limit of detection of 0.166 μM has enhanced sensitivity and selectivity for tracking hypochlorite both in vitro and in vivo.
2.Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning.
Dong LIANG ; Chen YU ; Zhao MA ; Xingye YANG ; Zhenzhen LI ; Xuhui DONG ; Xiaojun QIN ; Lupei DU ; Minyong LI
Acta Pharmaceutica Sinica B 2022;12(5):2429-2442
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.