Relationship between structure and P-glycoprotein inhibitory activity of dimeric peptides related to the Dmt-Tic pharmacophore.
Bioorg Med Chem Lett
; 22(6): 2192-4, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22365753
ABSTRACT
To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized, N(α),N(ε)-[(CH(3))(2)Mle-Tic](2)Lys-NH(2) and its D-Lys analog were found to exhibit potent P-gp inhibitory activity, twice that of verapamil, in doxorubicin-resistant K562 cells. Structure-activity studies indicated that the correct hydrophobicity and spacer length between two aromatic rings are important structural elements in this series of analogs for inhibition of P-gp.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Tetra-Hidroisoquinolinas
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Dipeptídeos
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article