Nature 230, 408 - 409 (09 April 1971); doi:10.1038/230408a0

Antischistosomal Action of Tubercidin administered after Absorption into Red Cells

J. J. JAFFE, E. MEYMARIAN & H. M. DOREMUS

Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont 05401

SCHISTOSOMES seem to depend primarily if not exclusively on the anabolism of preformed purines for their total purine nucleotide requirements (ref. 1 and our own unpublished observations). Among various purine analogues we tested against Schistosoma mansoni in vitro, tubercidin (7-deazaadeno-sine)² was the most active, causing early separation of paired adults, alterations of the muscular activity pattern, and inhibition of egg laying in the medium when present in a concentration as low as 10^-7 M. When administered to S. mansoni-infested mice either intraperitoneally or orally, tubercidin in effective dose regimens invariably caused 20–30% mortality. In an attempt to increase the margin of safety of this potentially useful antischistosomal agent, we considered the following facts in planning a new strategy of treatment. Schistosomes feed on blood cells, beginning about 2 weeks after cercarial penetration of the host³. Tubercidin is rapidly absorbed into red cells in vitro and is sequestered intracellularly in a phosphorylated form⁴. From 0.2–0.4 mg of tubercidin/ml. of whole blood can be so sequestered, and the longevity of tubercidin-containing red cells is unaffected⁴. We have investigated whether host red cells could deliver tubercidin to haematophagous forms of schistosomes, thereby increasing the selective toxicity of this antibiotic.

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