Enzymatic formation of potential anticancer and antiviral inosine analogues.

Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication. To acquire a broad spectrum of new candidate inosine analogues, a rapid, facile, quantitative and stereoselective method for deaminating potential antitumor and antiviral adenine analogues previously synthesized in our laboratory was developed. A novel 5'-adenylic acid deaminase, with relaxed substrate requirements, from Aspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehydes to their corresponding inosine analogues.

Synthesis and antileukemic activity of certain D-fucopyranosyl nucleosides.

Based upon previously discovered antileukemic properties of 9-beta-D-fucopyranosyladenine (1) in cell culture, four new nucleosides containing naturally occurring bases have been prepared from D-fucose. alpha-D-Fucopyranose tetraacetate was condensed with the silylated bases in either acetonitrile or 1,2-dichloroethane with tin(IV) chloride as the catalyst. The intermediate blocked nucleosides were obtained in crystalline form and deacetylated with methanolic sodium methoxide.

Angiogenic effects of macrophages isolated from ascitic fluid aspirated from women with advanced ovarian cancer.

The cellular components of ascitic fluid aspirated from the peritoneal cavity of women with advanced ovarian cancer were separated on a Ficoll gradient. Isolated macrophages, which were further purified, elaborated a growth factor which was mitogenic for human endothelial cells isolated from umbilical veins, arteries and the omental microvasculature in vitro, and was angiogenic in vivo. It is postulated that the macrophage-derived factor enhances tumor neovascularization of the widespread ovarian-derived peritoneal malignant lesions appearing in these patients, thus contributing to their rapid growth and metastasis, and the poor prognosis of the disease.

Antiproliferative activity of purine nucleoside dialdehydes against leukemia L1210 in vitro.

Sixteen purine nucleoside dialdehydes were assayed for antiproliferative activity against murine leukemia L1210 grown in vitro. These compounds either lacked the terminal hydroxymethyl group that is necessary in most cases for phosphorylation, and/or had stereochemically different configurations at one or two positions, or had some alteration in the purine ring structure. Among the latter were two lipophilic N6-benzyladenine containing dialdehydes, and two nucleoside dialdehydes with a bromine atom at C-8 of the purine.

Deoxycytidylate aminohydrolase activity in the Novikoff hepatoma is dependent on the localization of the tumor.

The activity of deoxycytidylate aminohydrolase, a pivotal enzyme for pyrimidine biosynthesis in mammalian tissue, is 100x greater in the Novikoff hepatoma harvested from the intraperitoneal cavity than in the same tumor excised from either subcutaneous or intramuscular sites. The increased enzyme activity in the intraperitoneal tumor is not due to an increase in protein synthesis, since there are no significant differences in enzyme activity between normal liver, and either the subcutaneous or intramuscular hepatomas. Evidence is presented which indicates that deoxycytidylate aminohydrolase activity, and the expression of alternate pathways of pyrimidine biosynthesis in the Novikoff hepatoma, is dependent on the localization of the tumor within the host.