Perezone and its phenyl glycine derivative induce cytotoxicity via caspases on human glial cancer cells.

The new phenyl glycine derivative of perezone was obtained in a single reaction step in ca. 80% yield which showed remarkable cytotoxic activity against the astrocytoma U-251 cell line. After 24 h of exposure, both perezone (IC₅₀ = 6.83 ± 1.64 µM) and its phenyl glycine derivative (2.60 ± 1.69 µM) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC₅₀ = 28.54 ± 1.59 and 31.87 ± 1.54 µM respectively). Both compounds induced cellular morphological changes (pyknosis or cytoplasmic vacuolization) and increased the expression of caspases 3, 8, and 9 genes related to apoptosis. In the acute toxicity study, phenyl glycine perezone (DL₅₀ = 2000 mg/Kg) demonstrated to be less toxic than perezone (DL₅₀ = 500 mg/Kg). Phenylglycine-perezone can envisage a beneficial therapeutic potential. [ABSTRACT FROM AUTHOR]