Search of vasopressin analogs with antiproliferative activity on small-cell lung cancer: drug design based on two different approaches.
Future Med Chem
; 10(8): 879-894, 2018 04 01.
Article
em En
| MEDLINE
| ID: mdl-29589487
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasopressinas
/
Proliferação de Células
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Carcinoma de Pequenas Células do Pulmão
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Argentina