Synthesis and cytotoxic activity of 4-N-carboxybutyl-5-fluorocytosyl-Arg-Gln-Trp-Arg-Arg-Trp-Trp-Gln-Arg-NH2

CSABA SOMLAI; CORRECHE ESTELA; OLIVELLA MONICA; TOLOSA LAIA; GOMEZ-LECHON MARÍA JOSÉ; DAMBI GYORGY; TOTH GABOR; BOTOND PENKE; ENRIZ R.D.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 22 p. 4233 - 4237

0960-894X

The chemical synthesis of 4-N-carboxybutyl-5-fluorocytosine (compound II) in solution phase starting from 5-fluorocytosine and the solid phase synthesis of Arg-Gln-Trp-Arg-Arg-Trp-Trp-Gln-Arg-NH2 attached to the 4-N-carboxybutyl-5-fluorocytosine residue at the N-terminus of the peptide (compound III) via peptide bond formation is reported. The target compound (compound III) exhibited a significant cytotoxic activity against a culture of HepG2 cells. In addition our results demonstrated that this new compound affect cell viability, produce mitochondrial dysfunction as well as interfere with intracellular calcium homeostasis control; leading to cell malfunction and death.