Eimeria tenella, E. necatrix, E. acervulina, and E. maxima: Anticoccidial activity of 1,6-dihydro-6-oxo-2-pyrazinecarboxylic acid 4-oxide

Matsuno, Toshimi; Kobayashi, Nobuo; Hariguchi, Fumio; Yamazaki, Toshiyuki; Imai, K.; Onaga, Hiroshi

doi:10.1016/0014-4894(84)90062-6

Cited by 10 publications

(3 citation statements)

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“…These findings suggest a possible key role for uridine in pyrimidine nucleotide synthesis by Eimeria. Interestingly, many uridine analogues inhibit the growth of Eimeria species [264][265][266].…”

Section: Eimeria Speciesmentioning

confidence: 99%

Purine and pyrimidine metabolism in parasitic protozoa

Hassan¹

1988

FEMS Microbiology Letters

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Section: Eimeria Speciesmentioning

confidence: 99%

Purine and pyrimidine metabolism in parasitic protozoa

Hassan¹

1988

FEMS Microbiology Letters

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“…The orotic acid analogue, 1,6-dihydro-6-oxo-2-pyrazinecarboxylic acid 4-oxide also known as carboxyemimycin (Fig. 3), exhibited marked anticoccidial activities against Eimeria tenella , E. necatrix , E. acervulina , and E. maxima (Matsuno et al, 1984). In Plasmodium falciparum , which are completely dependent on de novo pyrimidine metabolism, another orotate analogue, 5-fluoroorotate (Fig.…”

Section: Enzymes Of De Novo Pyrimidine Biosynthesismentioning

confidence: 99%

“…With the exception of 5-fluorinated pyrimidines (Jaffe, 1975; Pfefferkorn and Pfefferkorn, 1977; Howells et al, 1981; Gómez, and Rathod, 1990; Papageorgiou et al, 2004; Arakaki et al, 2008; Ali et al, 2013a and 2013b; Alzahrani et al, 2016a), and carboxyemimycin (1,6-dihydro-6-oxo-2-pyrazinecarboxylic acid 4-oxide) (Matsuno et al, 1984) none of the pyrimidine analogues tested were found to be effective against parasites. These results, however, should not discourage the testing of other and newer pyrimidine analogues as antiparasitic agents.…”

Section: Pyrimidine Analogues As Potential Antischistosomal Drugsmentioning

confidence: 99%

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Kouni

2017

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Schistosomes are responsible for the parasitic disease schistosomiasis, an acute and chronic parasitic ailment that affects more than 240 million people in 70 countries worldwide. It is the second most devastating parasitic disease after malaria. At least 200,000 deaths per year are associated with the disease. In the absence of the availability of vaccines, chemotherapy is the main stay for combating schistosomiasis. The antischistosomal arsenal is currently limited to a single drug, Praziquantel, which is quite effective with a single-day treatment and virtually no host-toxicity. Recently, however, the question of reduced activity of Praziquantel has been raised. Therefore, the search for alternative antischistosomal drugs merits the study of new approaches of chemotherapy. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Pyrimidine metabolism is an excellent target for such studies. Schistosomes, unlike most of the host tissues, require a very active pyrimidine metabolism for the synthesis of DNA and RNA. This is essential for the production of the enormous numbers of eggs deposited daily by the parasite to which the granulomas response precipitate the pathogenesis of schistosomiasis. Furthermore, there are sufficient differences between corresponding enzymes of pyrimidine metabolism from the host and the parasite that can be exploited to design specific inhibitors or “subversive substrates” for the parasitic enzymes. Specificities of pyrimidine transport also diverge significantly between parasites and their mammalian host. This review deals with studies on pyrimidine metabolism in schistosomes and highlights the unique characteristic of this metabolism that could constitute excellent potential targets for the design of safe and effective antischistosomal drugs. In addition, pyrimidine metabolism in schistosomes is compared with that in other parasites where studies on pyrimidine metabolism have been more elaborate, in the hope of providing leads on how to identify likely chemotherapeutic targets which have not been looked at in schistosomes.

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