Metabolism of adenosine analogues by Schistosoma mansoni and the effect of nucleoside transport inhibitors. 1987

M H el Kouni, and S Cha

Schistosoma mansoni incorporated tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, 7,9-dideaza-7-thiaadenosine and toyocamycin but not sangivamycin, 3'-deoxy-sangivamycin, or 1-methylformycin into their nucleotide pool after a 4-hr incubation in vitro. In contrast to mammalian systems, addition of nucleoside transport inhibitors nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), dilazep, or benzylacyclouridine had no significant effect on the pattern of incorporation of these adenosine analogues. Dipyridamole, on the other hand, reduced, but did not prevent, the incorporation of these analogues into the nucleoside 5'-triphosphate pool. These results suggest that the transport of purine nucleosides in schistosomes is different from that of their mammalian hosts. Therefore, coadministration of a specific nucleoside transport inhibitor with tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, toyocamycin, or 7,9-dideaza-7-thiaadenosine may result in high selective toxicity against schistosomes, as was the case with the combination of tubercidin plus NBMPR-P [el Kouni et al., Proc. natn. Acad. Sci. U.S.A. 80, 6667 (1983); el Kouni et al., Biochem. Pharmac. 34, 3921 (1985)], by protecting the host but not the parasite from the toxicity of these analogues.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D004109 Dilazep Coronary vasodilator with some antiarrhythmic activity. Asta C 4898,Biopropazepan Trimethoxybenzoate,Cormelian,C 4898, Asta,Trimethoxybenzoate, Biopropazepan
D004176 Dipyridamole A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752) Antistenocardin,Apo-Dipyridamole,Cerebrovase,Cléridium,Curantil,Curantyl,Dipyramidole,Kurantil,Miosen,Novo-Dipiradol,Persantin,Persantine,Apo Dipyridamole,Novo Dipiradol
D000241 Adenosine A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Adenocard,Adenoscan
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D012550 Schistosoma mansoni A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis. Schistosoma mansonus,mansonus, Schistosoma
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013868 Thioinosine Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503) 6-Mercaptopurine Riboside,NSC-4911,Ribosyl-6-mercaptopurine,6 Mercaptopurine Riboside,Riboside, 6-Mercaptopurine,Ribosyl 6 mercaptopurine

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