Download e-book for kindle: Analogues of Nucleic Acid Components: Mechanisms of Action by P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)

By P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)

ISBN-10: 3642855768

ISBN-13: 9783642855764

ISBN-10: 3642855784

ISBN-13: 9783642855788

The intent for the layout of structural analogues of a typical metabolite is that such compounds might intrude within the usage or functionality of the metabolite. A compound that is powerful during this recognize should be known as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor development, an antimetabolite may still adversely impact a few very important metabolic reactions within the parasite or parasitic tissue with out heavily endangering the host tissue. If a metabolic technique of the offending development isn't the same as that of the host, it's most likely that the metabolism or task of a compound, structurally with regards to a metabolite interested in that strategy, can also be diversified in those cells. Such modifications are important for devising powerful medicines with selective activities. Sulfanilamide, a structural analogue of para­ aminobenzoic acid, interferes with the usage of this metabolite within the synthesis of folic acid, a vital issue for development. micro organism synthesize their very own folic acid and are incapable of using exogenously on hand folic acid. notwithstanding, the placement is precisely contrary within the animal host. that's, animal tissues can't synthesize folic acid and are completely established upon exogenous assets. those modifications in metabolism make attainable using sulfanilamide as a selective inhibitor of development. different antibacterial or antiparasitic medications, resembling penicillin (BURCHALL, FERONE and HITCHINGS, 1965) and inhibitors of dihydrofolate reductase (HITCHINGS and BURCHALL, 1965; HITCHINGS, 1964; BURCHALL and HITCHINGS, 1965) have analogous fascinating selective toxicity effects.

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Extra resources for Analogues of Nucleic Acid Components: Mechanisms of Action

Example text

GTP --~DNA Th;o~G -~-> Th;'~GMP~'~GDP ~Tb;'~GTP _ _ _ _ _ _ _ _--;~ RNA IMP----r'---~XMP~GMP~DP Fig. 13. Metabolism of thio-G and the known sites of inhibition. The lines with affected sites ~ indicate of phosphoribosylpyrophosphate amidotransferase, the first enzyme in the de novo pathwa y of purine synthesis, the Ki value being 2 X 10- 4 M. With the accumulation of thio-GMP a significant inhibition of this enzyme in vivo has also been observed (SARTORELLI and LEPAGE, 1958). , 1967) is subject to inhibition by thio-GMP.

Likewise, a resistant tumor having a poor capacity to form ribonucleotide respond to the deoxynucleoside derivative only (LEPAGE, JUNGA and BOWMAN, 1964). Catabolism: The catabolism of thio-G in man, as well as in lower animals, follows the general pathway shown in Fig. 14 (ELlON, 1967). /! ;: --- - 2-Hydroxy-6-thiopurine~:::=~ 2-Hydroxy-6-methylthiopurine ~2'8-DihYdrOxL6-thiopurine (Thiouric acid) Fig. 14. Catabolic pathways of thio-G. Broken lines represent possible routes of conversion not definitely established (ELI ON, 1967) differences in these catabolic reactions in man and mouse.

As a matter of fact, the di- and triphosphates of ara-A have been shown to inhibit reduction of all four common ribonucleoside diphosphates to deoxyribonucleoside diphosphates with a partially purified enzyme system from rat tumor (MOORE and COHEN, 1967). The effects of ara-ADP and ara-ATP in this system appear to be quite comparable to those of dATP, except that dATP is five to eight times more active on a concentration basis. Interference with the reduction of CDP and possibly also of UDP is caused by the competition with ATP for the activation site.

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Analogues of Nucleic Acid Components: Mechanisms of Action by P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)


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