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

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 13; pp. 4233 - 4237
• Main Authors: Somlai, Csaba, Correche, Estela, Olivella, Monica, Tolosa, Laia, Lechon, Maria José Gomez, Dombi, György, Tóth, Gábor K, Penke, Botond, Enriz, Ricardo D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2012
• Subjects: Amino Acid Sequence; calcium; Calcium - metabolism; Cell Survival - drug effects; cell viability; cytotoxicity; death; Flucytosine - chemistry; Hep G2 Cells; homeostasis; Homeostasis - drug effects; human cell lines; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondria - physiology; Peptides - chemical synthesis; Peptides - chemistry; Peptides - toxicity; synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.05.045

The chemical synthesis of 4-N-carboxybutyl-5-fluorocytosine (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 (III) via peptide bond formation is reported. The target compound 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.