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

Abstract

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.

Graphical Abstract

Keywords:

• Phenyl glycine-perezone
• apoptosis
• cancer cell line
• natural product
• cytotoxic activity
• caspases

Acknowledgments

To Professor Raúl G. Enríquez for general advice; to MSc. Elizabeth Huerta (NMR), Dra. Adriana Romo (IR), and Dra. María del Carmen García (MS) and LURM (NMR-700 MHz) from Instituto de Química, UNAM; to Dirección de Investigación del Hospital Infantil de México Federico Gómez for general support; to SNI CONACyT awarded to MEC (66698), and honorary payment from CONACyT MAOM (CVU 603692, CONACyT-FOINS-307152) are gratefully acknowledged.

Author contributions

Marco A. Obregón-Mendoza designed and planned the research; Estévez-Carmona M. M. and Obregón-Mendoza M. A. contributed to experimental analysis, discussion of results, and the writing-editing final version. Ramírez-Apan M. T. and Vega-Miranda A. supplied tumoral cell lines and performed preliminary cytotoxicity essays. Arenas-Huertero F. and Zaragoza-Ojeda M. performed the cytotoxicity assays, the cell morphology analysis, and the caspase expression determination. Reynolds W.F. analyzed NMR spectra. All authors approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by CONACyT Project CONACyT-FOINS-307152 and PAPIIT, UNAM Project IT200720.