By P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)
The motive for the layout of structural analogues of a regular metabolite is that such compounds could intervene within the usage or functionality of the metabolite. A compound that's potent during this recognize might be referred to as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor development, an antimetabolite may still adversely have an effect on a few very important metabolic reactions within the parasite or parasitic tissue with no heavily endangering the host tissue. If a metabolic technique of the offending development isn't the same as that of the host, it really is most probably that the metabolism or job of a compound, structurally regarding a metabolite fascinated by that procedure, can be assorted in those cells. Such modifications are valuable for devising potent 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 to be had folic acid. besides the fact that, the placement is precisely contrary within the animal host. that's, animal tissues can't synthesize folic acid and are completely established upon exogenous resources. those alterations in metabolism make attainable using sulfanilamide as a selective inhibitor of progress. different antibacterial or antiparasitic medicinal drugs, reminiscent of 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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Additional info for Analogues of Nucleic Acid Components: Mechanisms of Action
Xyl-ATP exerts a slight inhibitory effect on the synthesis of DNA in extracts of TA3 cells (YORK and LEPAGE, 1966). The mechanism of action of xyl-A has not been thoroughly studied and it remains to be seen whether other important biological reactions requiring participation of ATP are inhibited by xyl-ATP. Chapter 3 Pyrimidines A. Metabolism of Pyrimidines Prior to a discussion of the biochemical mechanism of action of pyrimidine analogues it is desirable to outline briefly the normal metabolic reactions of pyrimidines.
Enzymatic formation of thio-GMP from thio-G and PRPP by guanine-hypoxanthine phosphoribosyltransferase has been 2-Amino-6-mercaptopurine (6-Thioguanine) 25 demonstrated (BROCKMAN, 1963). This nucleotide analogue has been reported to accumulate in much higher levels in some tumor cells than in normal tissues (MOORE and LEPAGE, 1958). , 1967). The reaction rate is less than one-hundredth of the rate obtained with GMP. However, work from laboratories of LEPAGE and colleagues (SAR TORELLI, LEPAGE and MOORE, 1958; of thio-G into DNA and RNA of neoplastic cells.
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. , 1962), while deamination and subsequent oxidation to thiouric acid occurs to only a small extent in man, but is the main pathway in the mouse (ELlON, 1967). Similar to the catabolism of 6-mercaptopurine, sulfate is a major end product in the degradative reactions of thio-G.