Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors.
Eur J Med Chem
; 89: 442-66, 2015 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-25462258
ABSTRACT
Modulation of Hsp90 C-terminal function represents a promising therapeutic approach for the treatment of cancer and neurodegenerative diseases. Current drug discovery efforts toward Hsp90 C-terminal inhibition focus on novobiocin, an antibiotic that was transformed into an Hsp90 inhibitor. Based on structural information obtained during the development of novobiocin derivatives and molecular docking studies, scaffolds containing a biphenyl moiety in lieu of the coumarin ring present in novobiocin were identified as new Hsp90 C-terminal inhibitors. Structure-activity relationship studies produced new derivatives that inhibit the proliferation of breast cancer cell lines at nanomolar concentrations, which corresponded directly with Hsp90 inhibition.
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MEDLINE
Assunto principal:
Benzamidas
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Compostos de Bifenilo
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Desenho de Fármacos
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Proteínas de Choque Térmico HSP90
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Proliferação de Células
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Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article