Disease relevance of CI 908

• Action of 3-deazaguanine in Escherichia coli [1].
• The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50 [2].
• In contrast to 3-deazaguanine and its ribosyl derivative, the nucleosides described in this paper were found to be inactive against Sarcoma 180 in mice at 100 mg/kg [3].
• In cytopathic effect inhibition studies, bluetongue virus was markedly inhibited by 3-deazaguanine and 3-deazauridine in Vero cells with moderate inhibition by the other agents [4].
• 3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity [5].

High impact information on CI 908

• 3-Deazaguanine inhibited both DNA and protein synthesis, and both log DNA synthesis and log protein synthesis correlated inversely with [3-deazaguanine] X t and directly with cell viability (P less than 0.001) [6].
• These data suggest that 3-deazaguanine is anabolized and incorporated into DNA, and that this incorporation is related to decreased DNA synthesis and cell death [6].
• Cell line TGR-3, deficient in hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) and resistant to 3-deazaguanine, also formed both metabolites [7].
• A new synthesis of certain 7-(beta-D-ribofuranosyl) and 7-(2-deoxy-beta-D-ribofuranosyl) derivatives of 3-deazaguanine via the sodium salt glycosylation procedure [8].
• The G to 3DG substitution at the primer terminus also decreased the formation of correct base pairs as well as incorrect base pairs [9].

Chemical compound and disease context of CI 908

• The hydrogen bonding interactions between the Klenow fragment of Escherichia coli DNA polymerase I with the proofreading exonuclease inactivated (KF(-)) and the minor groove of DNA were examined with modified oligodeoxynucleotides in which 3-deazaguanine (3DG) replaced guanine [9].

Biological context of CI 908

• Incorporation into DNA was linear versus [3-deazaguanine] X t and correlated inversely with cell viability (P less than 0.001) [6].
• The steady-state and pre-steady-state kinetics of DNA replication were measured with 10 different oligodeoxynucleotide duplexes in which 3DG was placed at different positions [9].
• Preclinical studies suggest that dezaguanine does not undergo deamination to 3-deazaxanthine, and is not metabolized by xanthine oxidase [10].
• Clinical pharmacokinetics of 3-deazaguanine [11].

Anatomical context of CI 908

• Pyrazofurin, 3-deazaguanine, and ribavirin inhibited both viral antigen expression and syncytium formation in HeLa cell cultures, as assessed by an indirect immunofluorescence assay [12].
• Finally, dezaguanine can cross the blood-brain barrier [10].
• The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal [5].

Associations of CI 908 with other chemical compounds

• Addition of certain purines or purine nucleosides can prevent dezaguanine cytotoxicity in vitro [10].
• Effects of 3-deazaguanosine and 3-deazaguanine on the growth and maturation of the human promyelocytic leukemia cell line, HL-60 [13].

Gene context of CI 908

• Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity [14].
• An expression of cellular transformation in chicken embryo fibroblast infected with Rous sarcoma virus (RSV) was inhibited by 3-deazaguanine (3-DG) [15].

Analytical, diagnostic and therapeutic context of CI 908

• DNA-directed actions of 3-deazaguanine: effects on DNA integrity and DNA elongation/ligation [16].
• Incorporation of 2-14C-labeled 3-deazaguanine into DNA and RNA, separated by Cs2SO4 density gradient centrifugation, was demonstrated [6].
• Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle [5].
• Determination of 3-deazaguanine in mice plasma by high-performance liquid chromatography [17].
• 3-deazaguanine, a candidate drug for the chemotherapy of breast carcinomas [18]?

References