8- azaguanine

This synthetic procedure was used without any significant changes for the preparation of the greatest number of derivatives of t -tria-zolo [4,5-d] pyrimidine. Roblin et prepared the aza analogs of the principal purine bases 8-azaguanine (151), 8-azaadenine (152), 8-azaxanthine (153), and 8-azahypoxanthine (154). By similar methods,... 

Sirianni SR, Huang CC. 1980. Comparison of induction of sister chromatid exchange, 8-azaguanine- and ouabain-resistant mutants by cyclophosphamide, ifosfamide and l-(pyridyl-3)-3,3-dimethyltriazene in Chinese hamster cells cultured in diffusion chambers in mice. Carcinogenesis 1 353-355. 

Not all analogues become active against cancer cells through incorporation into nucleic acid. Some analogues block the synthesis of normal purine and pyrimidine nucleotides for example, 8-azaguanine blocks guanosine monophosphate (GMP) synthesis and 6-mercaptopurine inhibits adenosine monophosphate (AMP) syn-thesis. 

S. Lu, Electrochemical determination of 8-azaguanine in human urine at a multi-carbon nanotubes modified electrode. Microchem. J. 77, 37-42 (2004). 

Azaguanine and thioguanine are catabolized by guanase, and both the purinethiones are degraded by xanthine oxidase. Methylation and demethylation is an important factor in the activity of the thiopurihes and certain adenine or adenosine analogues also. 

Azaguanine was the first purine analogue shown to be incorporated into polynucleotides [337] and, since its primary metabolic effect is on protein synthesis, the incorporation into RNA is considered the basis for its biologic activity [338]. In microbial systems 8-aza-adenine, 8-azahypoxanthine, 8-azaxanthine, and 5(4)-amino-l/f-l, 2, 3-triazole-4(5)-carboxamide are all incorporated into RNA as 8-azaguanylic acid [336]. 

It is of historical interest that Tetrahymena gelii, whose metabolism has been described in detail [387], is inhibited by 8-azaguanine [388] and other purine analogues [389, 390]. Of more importance to chemotherapy is the fact that pathogenic protozoa such as the trypanosomes respond in vitro to a number of... 

Although inactive against the Rous sarcoma in the standard post-infection test, 6-mercaptopurine, 2-aminoadenine, and 8-azaguanine inhibited the development of the tumour if given prior to infection of the chicks (417, 418]. 

Azaguanine is inhibitory to several experimental animal tumour systems [444], but is not highly active. Clinically its toxicity has been more apparent than its anticancer effects [362, 363]. 

One of the first demonstrations that acquired resistance could be circumvented was the inhibition of 5. faecalis resistant to 8-azaguanine by 8-azaxanthine. Thus, cells that possess xanthylic acid phosphoribosyltransferase activity could form 8-azaxanthylic acid, which was then converted to 8-azaguanylic acid and incorporated in nucleic acids as such [98]. 

Skopek, T. R., H. L. Liber, J. J. Krolewski, and W. G. Thilly, Quantitative Forward Mutation Assay in Salmonella typhimurium Using 8-Azaguanine Resistance as a Genetic Marker, Proc. Natl. Acad. Sci. U.S.A., 75, 410-414 (1978b). 

Liber, H.L. (1985) Mntation tests with Salmonella nsing 8-azaguanine resistance as the genetic marker. Prog. Mutat. Res., 5, 213-216... 

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