Bis-2(5H)-furanone derivatives as new anticancer agents: Design, synthesis, biological evaluation, and mechanism studies.
Yan-Cheng WuLiang CaoWen-Jie MeiHan-Qing WuShi-He LuoHai-Ying ZhanZhao-Yang WangPublished in: Chemical biology & drug design (2018)
New bis-2(5H)-furanone derivatives containing a benzidine core were synthesized via a one-step transition-metal-free reaction of benzidine with 5-substituted 3,4-dihalo-2(5H)-furanones. Their antitumor activities against various tumor cells have been evaluated by MTT assay. Among them, compound 4e exhibits significant inhibitory activity against C6 glioma cells with an IC50 value of 12.1 μm and low toxicity toward HaCaT human normal cells. Studies on the antitumor mechanism reveal that cell cycle arrest at S-phase in C6 cells is induced by compound 4e. Furthermore, investigations with electronic, fluorescence emission and circular dichroism spectra show that compound 4e can significantly interact with C6-DNA. These data indicate that DNA may be one of the potential targets for bis-2(5H)-furanone derivatives as anticancer drugs.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- induced apoptosis
- single molecule
- circulating tumor
- endothelial cells
- signaling pathway
- cell free
- endoplasmic reticulum stress
- case control
- molecular docking
- high throughput
- risk assessment
- machine learning
- dna methylation
- human health
- molecular dynamics simulations
- drug induced
- artificial intelligence
- pluripotent stem cells
- structure activity relationship
- solid state