Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens.
Bioorg Med Chem
; 23(15): 4150-4154, 2015 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-26178912
ABSTRACT
The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50=7.6, 4.7, and 4.0 µM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hyptis
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Artocarpus
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Proteínas Hedgehog
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article