Synthesis of uronic-noeurostegine--a potent bacterial ß-glucuronidase inhibitor.
Org Biomol Chem
; 9(22): 7807-13, 2011 Oct 26.
Article
en En
| MEDLINE
| ID: mdl-21952673
ABSTRACT
Inhibition of ß-glucuronidases has recently been shown to be useful in alleviating drug toxicity for common colon cancer chemotherapeutic CPT-11 (also called Irinotecan). We have prepared a new compound of the nortropane-type, uronic-Noeurostegine, and demonstrated that this is a competitive and potent E. coli ß-glucuronidase inhibitor, while inhibition of the mammalian ß-glucuronidase from bovine liver was found to be less significant. Although not intended, two other compounds having N-ethyl and N-(4-hydroxybutyl) substituents were also prepared in this study due to the sluggish debenzylation in the final step. The N-substituents are believed to come from reaction with the solvents used being ethanol and THF, respectively. These compounds also inhibited the two ß-glucuronidases albeit to a lesser extent compared to the parent compound. Noeurostegine and the three uronic-noeurostegines were additionally evaluated as inhibitors against a wide panel of glycosidases with the former showing potent inhibition of rat intestinal lactase and trehalase, whereas the latter was found to be inactive.
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1
Banco de datos:
MEDLINE
Asunto principal:
Química Farmacéutica
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Proteínas de Escherichia coli
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Inhibidores Enzimáticos
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Glucuronidasa
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Nortropanos
Límite:
Animals
Idioma:
En
Año:
2011
Tipo del documento:
Article