Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings.
Bioorg Med Chem Lett
; 27(17): 4199-4203, 2017 09 01.
Article
em En
| MEDLINE
| ID: mdl-28754364
ABSTRACT
The new lignano-9,9'-lactones (α,ß-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC50=12µM), however, it was inactive against HeLa cells (EC50>100µM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC50 values of 10µM and 9.4µM against HL-60 cells, respectively. Against HeLa cells, the EC50 value of the derivative 66 was 27µM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lignanas
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Furanos
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Halogênios
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Hidrocarbonetos Aromáticos
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article