Design, synthesis and anticancer activities of novel otobain derivatives.
Org Biomol Chem
; 14(1): 277-87, 2016 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-26593226
ABSTRACT
A series of novel racemic otobain derivatives was designed and synthesised using 2-piperonyl-1,3-dithianes in the conjugate addition-alkylation to 5H-furan-2-one, followed by cationic cyclisation. All the synthesised compounds were consequently evaluated for their anticancer activity against several human cancers in vitro. The efficacy of the most active compound 27g was comparable with etoposide, with IC50 values ranging from 1.06 µM to 4.16 µM in different cancer cell lines. Notably, compound 27g strongly induced cell cycle arrest and increased the expression of mitosis-specific markers MPM-2 and phosphorylated histone H3, but it did not trigger cell apoptosis. Further a colony formation assay showed that compound 27g effectively inhibited the anchor growth of lung cancer cells in a dose-dependent manner. More importantly, compound 27g at 40 mg kg(-1) significantly suppressed tumour volume (P < 0.01) and tumour weight (P < 0.05) in a human lung cancer cell xenograft mouse model without causing systematic toxicity in mice. Our findings indicated that compound 27g has significant potential for further drug development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Lignanas
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article