Structure-cytotoxic activity relationship of sesquilignan, morinol A.
Bioorg Med Chem Lett
; 23(17): 4923-30, 2013 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-23896495
ABSTRACT
The cytotoxic activities of sesquilignans, (7S,8S,7'R,8'R)- and (7R,8R,7'S,8'S)-morinol A and (7S,8S,7'S,8'S)- and (7R,8R,7'R,8'R)-morinol B were compared, showing no significant difference between stereoisomers (IC50=24-35 µM). As a next stage, the effect of substituents at 7, 7', and 7"-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18 (IC50=6-7 µM). In the research on the structure-activity relationship of 7"-position of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18, the most potent compounds were 7,7',7"-phenyl derivative 18 (IC50=6 µM) against HeLa cells. Against HL-60 cells, 7"-(4-nitrophenyl)-7,7'-phenyl derivative 33 and 7"-hexyl-7,7'-phenyl derivative 37 (IC50=5 µM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7'R,8'R)-morinol A. It was also confirmed that the 7'-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.
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Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Assunto principal:
Piranos
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Medicamentos de Ervas Chinesas
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Lignanas
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Antineoplásicos Fitogênicos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão