An acyclic enediyne with a furyl tethering group for efficient inhibition of tumor cell viability
An acyclic enediyne with a furyl tethering group and two pH-sensitive orthoester groups at the alkynyl termini was synthesized. The enediyne compound yielded free radicals, which can be further trapped by other atoms, under acidic conditions at ambient temperature. It exhibited high cytotoxicity towards tumor cells, and affected normal cells much less, while showing very low cytotoxicity to both types of cells once the furan group was reacted with a dienophile, 4-phenyl-1,2,4-triazoline-3,5-dione. Confocal laser scanning microscopy experiments showed that the derivation of the furan group dictated the cytosis of the enediyne molecules. The cytotoxicity of the enediyne molecules disappeared when cytosis was hindered. The introduction of a furyl tethering group into enediyne represents a new design strategy of “intelligent” antitumor antibiotics that can distinguish tumor and normal cells.