Analogues of Nucleic Acid Components: Mechanisms of Action - download pdf or read online

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 purpose for the layout of structural analogues of an ordinary metabolite is that such compounds might intervene within the usage or functionality of the metabolite. A compound that is powerful during this admire can be known as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor progress, an antimetabolite should still adversely impact a few important metabolic reactions within the parasite or parasitic tissue with out heavily endangering the host tissue. If a metabolic strategy of the offending development isn't the same as that of the host, it truly is most probably that the metabolism or task of a compound, structurally on the topic of a metabolite fascinated about that approach, can also be diversified in those cells. Such variations are invaluable for devising powerful medications 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 necessary issue for progress. micro organism synthesize their very own folic acid and are incapable of using exogenously on hand folic acid. notwithstanding, the location is precisely contrary within the animal host. that's, animal tissues can't synthesize folic acid and are totally established upon exogenous resources. those changes in metabolism make attainable using sulfanilamide as a selective inhibitor of progress. different antibacterial or antiparasitic medicines, similar to 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

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However, it is also possible that incorporation of the analogue into nucleic acids may have some role in the overall effect. Small amounts of incorporation of thio-GMP into both DNA and RNA of tumors have been observed and it has been suggested that the susceptibility of the tumors to the growth inhibitory activity of thio-G is directly related to the degree of incorporation of the analogue into DNA (LEPAGE, 1960). Mecca lymphosarcoma cells are resistant to exposure to thio-G, although large amounts of thio-GMP accumulate and there is little incoporation of the analogue into DNA (LEPAGE, JUNGA and BOWMAN, 1964).

The sites of action and the metabolic fate of allopurinol is outlined in Fig. 15. The analogue is both an inhibitor of, and a substrate for xanthine oxidase. , 1966). 28 Purines Conversion of allopurinol to oxoallopurinol is catalyzed by xanthine oxidase, and oxoallopurinol is also an inhibitor of the enzyme (ELION, TAYLOR and HITCHINGS, 1964). Both of these forms of the inhibitor are cleared rapidly by mouse and dog kidney. ~l-Ribosyl(also called Alloxanthine) oxoallopurinol 7- RilsYl-oxoallopurinol Fig.

In the catabolic process, DNA and RNA are degraded by ribonucleases and deoxyribonucleases, of which there are many types, to ultimate and respective products of deoxyribo- and ribonucleoside monophosphates. The nucleoside monophosphates are dephosphorylated to nucleosides by various specific and nonspecific phosphatases. The nucleosides are then split to free bases, presumably by the action of nucleoside phosphorylases. The stages in the breakdown of pyrimidines are shown in Fig. 24. The catabolism is carried out exclusively through uracil and thymine.

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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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