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 & PLUSMN; 1.64 & mu;M) and its phenyl glycine derivative (2.60 & PLUSMN; 1.69 & mu;M) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC50 = 28.54 & PLUSMN; 1.59 and 31.87 & PLUSMN; 1.54 & mu;M 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.