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

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 antiprolifera...

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Bibliographic Details
Published in:Future medicinal chemistry 2018-04, Vol.10 (8), p.879-894
Main Authors: Pifano, Marina, Garona, Juan, Sobol, Natasha T, Albertó, Marina, Alonso, Daniel F, Ripoll, Giselle V
Format: Article
Language:English
Subjects:
antiproliferative
AVP
drug discovery
evolutionary approach
SAR studies
V2R agonists
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Summary: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. We designed two novel analogs; dDInotocin (dDINT, insect analog), and [V Q ]dDAVP, and demonstrated the importance of the dDAVP conformational loop for its antiproliferative activity. [V Q ] dDAVP showed major cytostatic effect on lung cancer cells than dDAVP and its cytostatic effect was abolished by V2R blockade. Combination of these strategies could provide the basis for future studies for the development of improved compounds with potential therapeutic applications.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2017-0178