Synthesis and cytotoxic activity of 4-N-carboxybutyl-5-fluorocytosyl-Arg-Gln-Trp-Arg-Arg-Trp-Trp-Gln-Arg-NH₂.
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-NH(2) 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.
Department of Medical Chemistry, Faculty of General Medicine, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Csaba
C
Somlai
Estela
E
Correche
Monica
M
Olivella
Laia
L
Tolosa
Maria José Gomez
MJ
Lechon
György
G
Dombi
Gábor K
GK
Tóth
Botond
B
Penke
Ricardo D
RD
Enriz
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005437:Flucytosine / Q000737:chemistry*; D056945:Hep G2 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D010455:Peptides; D005437:Flucytosine; D002118:Calcium