ISSN:
1420-908X
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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 μM). They were also selectively cytotoxic to MOLT-4 lymphoblasts in the presence of a nontoxic amount (10 μM) 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-thienyl-methyl)guanine; PD 119,229) has an IC50 of 0.17 μM (Ki=0.067 μM), significantly more potent than the known standard, 8-aminoguanosine (IC50=1.40 μM). Thus it represents the most potent PNP inhibitor known to date when tested without limiting the concentration of inorganic phosphate.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01966482