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Pathways of nucleotide metabolism in schistosoma mansoni—VII

1977; Elsevier BV; Volume: 26; Issue: 20 Linguagem: Inglês

10.1016/0006-2952(77)90158-7

1873-2968

Alfred W. Senft, Gerald W. Crabtree,

Digestive system and related health

Twelve analogs of adenosine or its related purines have been tested as single agents or in combinations as possible antischistosomal compounds. Measurements were made of the effect of these drugs on the anabolism and catabolism of [8-14C]adenosine by Schistosoma mansoni in vitro. Based on the degree of inhibition of biosynthesis of adenine and guanine nucleotides by intact worms. the best currently available purine analogs are 7-deaza-adenosine (tubercidin) and N6-phenyladenosine. These drugs reduced the total synthesis of nueleotides to 30 and 25 per cent, respectively, of controls. Blockade of the catabolic pathway (adenosine deaminase) by coformycin resulted in significantly increased synthesis of adenine nucleotides rather than the expected decrease. Thus, adenosine kinase must play a more prominent role in nucleotide synthesis than had been previously estimated. The implications of these findings in the development of new anti-schistosomal drugs are discussed.