Search of vasopressin analogs with antiproliferative activity on small-cell lung cancer: drug design based on two different approaches

PIFANO, MARINA; GARONA, JUAN; SOBOL, NATASHA T; ALBERTÓ, MARINA; ALONSO, DANIEL F; RIPOLL, GISELLE V

Future Medicinal Chemistry

Future Science and Newlands Press

Año: 2018 vol. 10 p. 879 - 894

1756-8919

AIM:Development of compounds with therapeutic application requires the interaction of different disciplines. Several tumors express vasopressin (AVP; arginine vasopressin) receptors with contrasting effects depending on receptor subtype. Desmopressin (dDAVP) is an AVP-selective analog with antiproliferative properties. In this work, an evolutionary approach and a rational strategy were applied in order to design novel AVP analogs.RESULTS:We designed two novel analogs; dDInotocin (dDINT, insect analog), and [V4Q5]dDAVP, and demonstrated the importance of the dDAVP conformational loop for its antiproliferative activity. [V4Q5] dDAVP showed major cytostatic effect on lung cancer cells than dDAVP and its cytostatic effect was abolished by V2R blockade.CONCLUSION:Combination of these strategies could provide the basis for future studies for the development of improved compounds with potential therapeutic applications