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 reason for the layout of structural analogues of a standard metabolite is that such compounds may perhaps intervene within the usage or functionality of the metabolite. A compound that's powerful during this appreciate can be referred to as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor progress, an antimetabolite should 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 means of the offending development isn't like that of the host, it really is most likely that the metabolism or job of a compound, structurally with regards to a metabolite focused on that strategy, may also be diversified in those cells. Such adjustments are beneficial 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 vital issue for progress. micro organism synthesize their very own folic acid and are incapable of using exogenously on hand folic acid. although, the placement is precisely contrary within the animal host. that's, animal tissues can't synthesize folic acid and are completely based upon exogenous assets. those transformations in metabolism make attainable using sulfanilamide as a selective inhibitor of progress. different antibacterial or antiparasitic medicines, corresponding 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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Additional info for Analogues of Nucleic Acid Components: Mechanisms of Action

Example text

In addition to the above major inhibitory site, there are other reactions which are known to be affected by xyl-A. It is as effective as adenosine as a feedback inhibitor of purine synthesis in mice by preventing 5' -phosphoribosyl-N-formylglycineamide formation. The feedback inhibition is probably not significant in vivo since adenosine cannot produce the increased survival times observed in mice treated with xyl-A. Xyl-ATP exerts a slight inhibitory effect on the synthesis of DNA in extracts of TA3 cells (YORK and LEPAGE, 1966).

Conditions whim enhance the incorporation of the analogue into RNA are also found to increase breakdown of polyribosomes (K WAN and WEBB, 1967). Pulse labeling studies with radioactive amino acid have suggested that the monomers and dimers are inactive in vivo, while the residual polyribosomes in the livers of the treated animals incorporate the isotope at a near normal rate (KWAN and WEBB, 1967). The apparent selective effect of aza-G on certain polyribosomes and not on others may possibly be related to the half-lives of different mRNAs or to the location or amount of aza-G in those species of RNA (KWAN and WEBB, 1967).

Reduction of the two pyrimidine ribonucleoside diphosphates (UDP and CDP) to the corresponding deoxyribonucleoside diphosphates is activated by ATP. One of the products, dUDP is converted to dTTP through a sequence of reactions. The initial concentrations of dTTP stimulates the reduction of UDP or CDP. However, an increase in its concentration results in an inhibition of the reactions. It is also interesting to note that the activity of carbamyl phosphate synthetase, the first enzyme in the de novo pathway, is significantly affected by a number of purine and pyrimidine nucleotides (ANDERSON and MEISER, 1966).

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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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