Synthesis and biological evaluation of 2,5-disubstituted furan derivatives as P-glycoprotein inhibitors for Doxorubicin resistance in MCF-7/ADR cell.
Eur J Med Chem
; 151: 546-556, 2018 May 10.
Article
em En
| MEDLINE
| ID: mdl-29656198
ABSTRACT
Multidrug resistance (MDR) is a tendency in which cells become resistant to structurally and mechanistically unrelated drugs, which is mediated by P-glycoprotein (P-gp). It is one of the noteworthy problems in cancer therapy. As one of the most important drugs in cancer therapy, doxorubicin has not good effectiveness if used independently. So targeting the P-gp protein is one of the key points to solve the MDR. Three series of furan derivatives containing tetrahydroquinoline or tetrahydroisoquinoline were designed and synthesized as P-gp inhibitors in this paper. Compound 5m containing 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline possessed good potency against P-gp (EC50â¯=â¯0.89⯱â¯0.11⯵M). The preliminary structure-activity relationship and docking studies demonstrated that compound 5m would be great promise as a lead compound for further study. Most worthy of mention is drug combination of doxorubicin and 5m displayed antiproliferative effect of about 97.8%. This study provides highlighted P-gp inhibitor for withstanding malignant tumor cell with multidrug resistance especially doxorubicin resistance setting the basis for further studies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Doxorrubicina
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Resistencia a Medicamentos Antineoplásicos
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Tetra-Hidroisoquinolinas
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Furanos
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Antibióticos Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China