By P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)
The cause for the layout of structural analogues of a standard metabolite is that such compounds could intrude within the usage or functionality of the metabolite. A compound that's powerful during this appreciate might be referred to as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor progress, an antimetabolite may still adversely impact 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 progress isn't like that of the host, it's most probably that the metabolism or job of a compound, structurally concerning a metabolite fascinated about that technique, may also be various in those cells. Such changes are priceless 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, an important 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 strictly contrary within the animal host. that's, animal tissues can't synthesize folic acid and are completely based upon exogenous assets. those adjustments in metabolism make attainable using sulfanilamide as a selective inhibitor of progress. different antibacterial or antiparasitic medications, akin 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
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). From the above discussion it can be concluded that the inhibition of protein synthesis by aza-G is related to its incorporation into one or more species of RNA, thus rendering them defective in their functions.
Several ascites cell tumors which are insensitive to the analogue, are known to possess a kinase system for the conversion of thioguanosine or deoxythioguanosine to the nucleotide form and respond somewhat to their effects. 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).
Coli DNA polymerase by ara-ATP suggests that DNA synthesis is inhibited by some other mechanism. 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.
Analogues of Nucleic Acid Components: Mechanisms of Action by P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)