8-Amino-9-substituted guanines: potent purine nucleoside phosphorylase (PNP) inhibitors.
Agents Actions
; 21(3-4): 253-6, 1987 Aug.
Article
em En
| MEDLINE
| ID: mdl-3120506
ABSTRACT
A series of 8-amino-9-substituted guanines was synthesized and their activity evaluated against human purine nucleoside phosphorylase (PNP). All compounds were found to be potent inhibitors of human PNP (IC50s 0.17-126 microM). They were also selectively cytotoxic to MOLT-4 lymphoblasts in the presence of a nontoxic amount (10 microM) of the PNP substrate, 2'-deoxyguanosine (GdR). The most potent of these analogs, 2,8-diamino-1,9-dihydro-9-(2-thienylmethyl)-6H-purin-6-one (8-amino-9-(2-thienylmethyl)guanine; PD 119,229) has an IC50 of 0.17 microM (Ki = 0.067 microM), significantly more potent than the known standard, 8-aminoguanosine (IC50 = 1.40 microM). Thus it represents the most potent PNP inhibitor known to date when tested without limiting the concentration of inorganic phosphate.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentosiltransferases
/
Purina-Núcleosídeo Fosforilase
/
Guanina
Limite:
Humans
Idioma:
En
Revista:
Agents Actions
Ano de publicação:
1987
Tipo de documento:
Article