Bis-2(5H)-furanone Derivatives as New Anticancer Agents: Design, Synthesis, Biological Evaluation and Mechanism Studies

Abstract

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.

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The bis-2(5H)-furanone derivatives containing a benzidine core are designed and easily obtained via a one-step transition-metal-free reaction, which develops new chemical scaffolds with significant inhibitory activity against C6 glioma cells via binding C6-DNA.

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