6,6'-Dihydroxythiobinupharidine as a poison of human type II topoisomerases.
Bioorg Med Chem Lett
; 29(15): 1881-1885, 2019 08 01.
Article
en En
| MEDLINE
| ID: mdl-31182315
ABSTRACT
A number of natural products with medicinal properties increase DNA cleavage mediated by type II topoisomerases. In an effort to identify additional natural compounds that affect the activity of human type II topoisomerases, a blind screen of a library of 341 Mediterranean plant extracts was conducted. Extracts from Nuphar lutea, the yellow water lily, were identified in this screen. N. lutea has been used in traditional medicine by a variety of indigenous populations. The active compound in N. lutea, 6,6'-dihydroxythiobinupharidine, was found to enhance DNA cleavage mediated by human topoisomerase IIα and IIß â¼8-fold and â¼3-fold, respectively. Mechanistic studies with topoisomerase IIα indicate that 6,6'-dihydroxythiobinupharidine is a "covalent poison" that acts by adducting the enzyme outside of the DNA cleavage-ligation active site and requires the N-terminal domain of the protein for its activity. Results suggest that some of the medicinal properties of N. lutea may result from the interactions between 6,6'-dihydroxythiobinupharidine and the human type II enzymes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Extractos Vegetales
/
ADN-Topoisomerasas de Tipo II
/
Alcaloides
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos