Nucleic Acid Precursors

Its action is based on differential requirement between host and parasite for nucleic acid precursors involved in growth as it selectively inhibits plasmodial dihydrofolate reductase. 

The use of radiolabeled nucleosides as markers for anticancer activity has become a popular method due to the commercial availability of such compounds. The technique is based upon the knowledge that cells rendered unable to replicate or killed by the anticancer agent are unable to effectively incorporate nucleic acid precursors into their DNA or RNA structure. Therefore, a decrease in cell viability correlates with a decrease in radioactivity relative to a control cell population. Although specific procedures differ, the basic technique involves the incubation of tumor cells in the presence of the radiolabeled compound with or without anticancer agent followed by scintillation counting to determine the radioacti vity of the samples. 

The use of radi olabeled nucleic acid precursors, primarily tritiated thymidine or (deoxy)uridine, however, is subject to numerous drawbacks. Nevertheless, the use of radiolabeled precursors have provided some promising clinical correlation data [174]. 

Although the radiolabeled nucleic acid precursor assays described above produce accurate and reproducible quantification of the number of viable cells in a sample, Mosmann [187] sought to develop a more rapid assay capable of handling large numbers of samples. A colorimetric technique was developed based upon the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetra-zolium bromide, or MTT. Early studies of MTT by Slater et al. [188] determined that when the MTT tetrazolium salt interacts with the dehydrogenase enzymes... 

Hydroxyurea. It is believed that hydroxyurea (Hydrea) impairs DNA synthesis by inhibiting a specific enzyme (ribonucleoside reductase) involved in synthesizing nucleic acid precursors.11 The uses of hydroxyurea are listed in Table 36-7. 

A rapid semiautomated microdilution method for the microbiological assay of the chloroquine has been developed by Desgardins (26). Antimalarial activity of chloroquine may be studied against cultured Plasmodium falciparum, microplates are used to prepare serial dilution of the drug. Parasites obtained from continuous stock cultures are subcultured in the micro-plates for 42 h. Inhibition of uptake of a radio labeled nucleic acid precursor by parasites serves as the indicator of antimicrobial activity. 

Nesterenko, E.P. et al. Separation of nucleic acid precursors on an amphoteric surfactant modified monolith using combined eluent flow, pH and concentration gradient. J. Sep. Set 2007, 30, 2910-2916. 

Booden, T., and Hull, R. W. (1973). Nucleic acid precursor synthesis by Plasmodium lophurae parasitizing chicken erythrocytes. Exp. Parasitol. 34,220-228. 

Sherman, I. W. (1977b). Transport of amino acids and nucleic acid precursors in malaria parasites. Bull. World Health Organ. 55, 211-225. 

Study on electron transfer of nucleic acid precursors and their modified structure 01MI125. 

Pyrimethamine is a folic-acid antagonist its therapeutic action is based on differential requirements between host and parasite for nucleic acid precursors involved in growth as it selectively inhibits plasmodial dihydrofolate reductase. Pyrimethamine inhibits the enzyme dihydrofolate reductase that catalyzes the reduction of dihydrofolate to tetrahydro-folate. This activity is highly selective against plasmodia and Toxoplasma gondii. It does not destroy gametocytes but arrests sporogony in the mosquito. Pyrimethamine possesses a blood schizonticidal, and some tissue schizonticidal activity may be slower than that of 4-amino-quinoline compounds. 

Figure 15.23 Nucleic acid precursors and their linkage. A, In the cell, nucleic acids are constructed from nucleoside triphosphates, precursors of the mononucleotide units. Each one consists of an N-containing base (structure not shown), a sugar, and a triphosphate group. In RNA (fop), the sugar is ribose in DNA, it is 2 -deoxyribose (C atoms of the sugar are denoted by a number primed, e.g.,...

Because methionine synthase is the only mammalian enzyme known to act on 5-methyltetrahydrofolate, the decreased intracellular activity of this enzyme causes 5-methyltetrahydrofolate to accumulate, at the expense of depleted pools of the other tetrahydrofolate coenzymes. Thus, even though total folate levels may seem ample, there is a functional folate deficiency, with insufficient levels of the formyl and methylene derivatives needed for synthesis of nucleic acid precursors. 

Chen, S. N. and Howells, R. E. (1981) Brugia pahangv. uptake and incorporation of nucleic acid precursors by microfilariae and macrofilariae in vitro. Exp. Parasitol. 51 296-306. 

Reeves, R. E. and West, B. (1980) Entamoeba histolytica nucleic acid precursors affecting axenic growth. Exp. Parasitol. 49 78-82. 

It is required for the synthesis of the amino acid methionine and the nucleic acid precursors the purines and pyrimidines. The RDA for folic acid is only about... 

Coumarin reduced labeled glucose incorporation and carbohydrate and protein content of the cytoplasm of Pythium, but enzymes related to the metabolism of cell wall polysaccharides were not affected [296]. It has been reported that moulds are more sensitive to coumarin when they are cultured on the simple synthetic nutrient medium than on the yeast water [140]. This suggests that coumarin blocks the synthesis of an unknown metabolite of ndamental importance. Coumarin was found to affect the level of a variety of free amino acids present in a cell. In addition, some nucleic acid precursors partially reverse the coumarin-induced inhibition of maize mesocotyle [131]. The stimulation of germination and growth caused by coumarin in low concentrations may be assumed as a supercompensation mechanism. 

Uracil mustard is not a uracil antagonist for E. coli Bu, which requires this nutrilite [479]. However, in rats with Walker 256 carcinosarcoma, incorporation of uracil-2- C into the RNA of intracellular tumour and spleen fractions is markedly inhibited [488]. UracU mustard also inhibits the incorporation of nucleic acid precursors into RNA and markedly inhibits DNA synthesis in tissues of A/J mice [489]. Inhibition of arginine incorporation into nuclear proteins was likewise noted [490]. 

The influence of vitamin E deficiency on nucleic acid metabolism has been investigated in rats, rabbits, and monkeys. The concentrations of both RNA and DNA are elevated in skeletal muscle and bone marrow. From studies with a variety of radioactive nucleic acid precursors it is concluded that vitamin E deficiency leads to an increased rate of DNA synthesis in rabbit skeletal muscle and in monkey skeletal muscle and bone marrow. These changes in nucleic acid metabolism may be related to the... 

H7 Hashimoto, S. Effects of nucleic acid precursors on liver injuries. I. Treatment of liver injury induced by low protein, amino acid imbalanced diet with AICA and AICA orotate in massive doses. J. Vitaminol. 13, 9-18 (1976)... 

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