Anita T. Shortnacy

Metabolism and Metabolic Effects of Halopurine Nucleosides in Tumor Cells in Culture

Abstract Within a series of halo derivatives of adenosine, deoxyadenosine and arabinosyladenine attempts have been made to correlate structure with cytotoxicity, substrate activity for adenosine deaminase and nucleoside kinases, and efficacy of the corresponding nucleotides against target enzymes.

A comparison of two methods for the preparation of 3-Deazapurine ribonucleosides

The reaction of the trimethylsilyl derivative of 4,6-dichloroimidazo[4,5-c]pyridine with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide gave four nucleosides-the α- and β-anomers of the 1-isomer and the α- and β-anomers of the 3-isomer (3.9:2.7:1.5:1). In contrast, the fusion reaction of 4,6-dichloroimidazo[4,5-c ]pyridine with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose gave a high yield of the 1-β-isomer, which was converted to the known 3-deazaadenosine (4-amino-l-β-D-ribofuranosylimidazo[4,5-c]pyridine).

Identification of metabolites of 9-β-d-arabinofuranosyl-2-fluoroadenine, an antitumor and antiviral agent

Analysis of blood from a dog given a 400 mg/m2 dose of 9-beta-D-arabinofuranosyl-2-fluoroadenine (2-F-araA) led to the identification of parent drug and a major metabolite, 9-beta-D-arabinofuranosyl-2-fluorohypoxanthine. 2-Fluoroadenine, a toxic derivative of 2-F-araA, was not detected in blood within the limits of detection, suggesting that parent drug was absorbed and distributed without systemic exposure to this toxic derivative. Parent drug, 2-fluoroadenine, and 9-beta-D-arabinofuranosyl-2-fluorohypoxanthine were identified in urine of dog, monkey, and mouse.

Synthesis and Antiviral Evaluation of Adenosine-N1-Oxide and 1-(Benzyloxy) Adenosines

Abstract The antiviral activity of adenosine-N1-oxide (1) and a variety of substituted 1-(benzyloxy) adenosines (2) has been re-investigated and significant in vitro activity vs. Vaccinia virus has been shown. In vivo activity in mice has also been demonstrated.

8-Substituted Purine Ribosides: Synthesis and Biological Activity

Abstract The syntheses of a series of 8-substituted purine ribofuranosides are described. Reductive deaminalion of 8-bromoadenosine triacetate (1) provides the key intermediate (2) for subsequent displacement reactions. Four compounds show significant activity in two cell culture Screens.