Unique bioactivation of tiazofurin--studies with resistant cells.
Indian J Biochem Biophys
;
1989 Jun; 26(3): 160-5
Artigo
em Inglês
| IMSEAR
| ID: sea-27729
ABSTRACT
Using resistant cells mechanism of action of new oncolytic nucleoside, tiazofurin (2-beta-D-ribofuranosyl thiazole-4 carboxamide, RTC) was studied in tissue cultured cells of Chinese Hamster Ovary cells (CHO-cells). Tiazofurin got converted in CHO-cells to tiazofurin-monophosphate and to NAD-analogue, a potent inhibitor of inosinate dehydrogenase. Resistant cells produced tiazofurin-5'-monophosphate in vitro but had a much reduced capacity to produce NAD-analogue, indicating absence of any effect of tiazofurin on incorporation of [14C]formate into guanine, inhibition of inosinate dehydrogenase as well as GTP levels in resistant cells. Using competition with various possible substrates it is found that the initial tiazofurin metabolism is catalysed by nicotinamide nucleoside kinase and NAD-analog formation is mediated by NAD-pyrophosphorylase. Decreased activity of the latter enzyme found in tiazofurin resistant cells not only inhibited the NAD analog formation from tiazofurin-5'-monophosphate but also the NAD-formation from nictotinamide-5'-monophosphate.
Texto completo:
DisponíveL
Índice:
IMSEAR (Sudeste Asiático)
Assunto principal:
Ribavirina
/
Ribonucleosídeos
/
Resistência a Medicamentos
/
Biotransformação
/
Linhagem Celular
/
Animais
/
Antimetabólitos Antineoplásicos
Idioma:
Inglês
Revista:
Indian J Biochem Biophys
Ano de publicação:
1989
Tipo de documento:
Artigo
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