Antiproliferative effect of 1-deamino-8-D-arginine vasopressin analogs on human breast cancer cells: impact of substitutions at the conformational peptide loop

IANUCCI N.; RIPOLL G. V.; GARONA J.; CASCONE O.; CICCIA G.; GOMEZ D.E.; ALONSO D.F.

Future Medicinal Chemistry

Future Science Ltd

Año: 2011 vol. 3 p. 1987 - 1993

1756-8919

Desmopressin (dDAVP), a synthetic nonapeptide derivative of arginine vasopressin, is a safe antidiuretic and hemostatic compound which acts as a selective agonist for the vasopressin V2 membrane receptor (V2R). It is known that dDAVP can inhibit progression of residual metastatic cells in preclinical models. Among other mechanisms, the compound induces an agonist effect on V2R present in tumor cells. Results/Discussion: Looking for novel analogs with improved antitumor activity, positions 4 and 5, at the conformational peptide loop, were punctually substituted. The analog [V4Q5]dDAVP exhibited a significantly higher antiproliferative effect than dDAVP in cultures of MCF-7, a V2R-expressing human breast carcinoma cell line. The chiral isomer of this analog and tetrapeptide fragments corresponding to the loop region were also assessed. Conclusion: Preclinical evaluation of the antitumor activity of [V4Q5]dDAVP in animal models is warranted.