Effects of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (NSC-407347), An alkylating agent derived from 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388)

Mizuno, N.; Decker, Richard W.; Zakis, Baiba

doi:10.1016/0006-2952(75)90182-3

Cited by 19 publications

(4 citation statements)

References 15 publications

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“…Similarly, the triazeno moiety of the anti-HIV drug zidovudine (AZT) is also metabolized by reduction to form the amine metabolite AMT in a reaction that is at least partially catalyzed by cytochrome P450 reductase ( − ). Additionally, the 1-aryl-3,3-dimethyltriazenes are antitumor compounds whose action lies in their capacity to alkylate DNA ( , ). It has been postulated that decomposition of their monodemethylated metabolites produces anilines and diazomethane, but alkyl radicals could also be invoked in this process as has been shown in these studies for DPT.…”

Section: Discussionmentioning

confidence: 99%

Reduction of 1,3-Diphenyl-1-triazene by Rat Hepatic Microsomes, by Cecal Microflora, and in Rats Generates the Phenyl Radical Metabolite: An ESR Spin-Trapping Investigation

Mason

et al. 2000

Chem. Res. Toxicol.

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An ESR spin-trapping technique was used to determine whether free radical metabolites are formed as a result of the reduction of 1, 3-diphenyl-1-triazene (DPT) in vivo and in vitro by components of the cytochrome P450 (P450) mixed-function oxidase system in microsomes or by gut microflora in anaerobic cecal incubations. The ESR spectrum of the DMPO-phenyl radical adduct was detected in a microsomal incubation containing DPT, DMPO, and NADPH with the following hyperfine coupling constants: a(N) = 15.95 G and = 24.37 G. The amplitude of the spectrum from the phenyl radical adduct generated in microsomal incubations of DPT with DMPO and NADPH was not attenuated by the P450 inhibitor 1-aminobenzotriazole (ABT) or by carbon monoxide, indicating that P450 is not significantly involved in phenyl radical formation. The formation of a DMPO-phenyl radical adduct was also catalyzed by recombinant human cytochrome P450 reductase. Addition of anti-rat P450 reductase antibody led to an attenuation of the signal in incubations containing either microsomes or reductase. Low concentrations of DMPO-phenyl radical adducts were detected by ESR in the toluene extract of cecal contents containing DPT and the spin trap. In the in vivo experiments with rats treated with DPT and the spin trap DMPO, the six-line ESR signal of the DMPO-phenyl radical adduct was readily detected in bile 40-60 min after rats were treated with DPT and DMPO. The results show for the first time that the phenyl radical is formed by the reduction of DPT and may indicate a toxic potential for this chemical.

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Section: Discussionmentioning

confidence: 99%

Reduction of 1,3-Diphenyl-1-triazene by Rat Hepatic Microsomes, by Cecal Microflora, and in Rats Generates the Phenyl Radical Metabolite: An ESR Spin-Trapping Investigation

Mason

et al. 2000

Chem. Res. Toxicol.

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“…This begs the question: what is the difference between bolus and fractionated regimens using TMZ? The relatively inefficient in vivo selection of MGMT P140K gene-modified cells, using a fractionated drug treatment regimen, is potentially due to the repair kinetics of a variety of DNA adducts following O 6 BG and TMZ treatment (42)(43)(44)(45)(46)(47). Importantly, in both cases in which we efficiently increased relatively low levels of MGMT P140K gene marking in pigtailed macaques with a provirus copy number of approximately 0.04 (Figure 6), we used O 6 BG-2X and BCNU without prior O 6 BG and TMZ treatment.…”

Section: Figurementioning

confidence: 99%

Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates

Beard¹,

Trobridge²,

Ironside³

et al. 2010

J. Clin. Invest.

102

132

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“…By using an ALS method, the PARAFAC algorithm minimizes a loss function which is a sum of squared residuals (SSR) expressed as: (6) where e ijk is the (i, j, k)-th element of E I×J×K . Actually, for trilinear resolution it is only necessary that matrices X and Y are full rank matrices for their column spaces, i.e.…”

Section: Trilinear Model and Resolution Algorithmsmentioning

confidence: 99%

“…The biological activity of DR results from its binding interaction with DNA; this inhibits cellular DNA-and RNA-dependent replication and transcription processes [4,5,6,7]. Studies of binding interaction are, therefore, valuable not only for understanding how proteins recognize and bind to specific DNA sequences, but also for guiding the design of new drugs [8].…”

Section: Introductionmentioning

confidence: 99%

Competitive interaction of the antitumor drug daunorubicin and the fluorescence probe ethidium bromide with DNA as studied by resolving trilinear fluorescence data: the use of PARAFAC and its modification

et al. 2002

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The competitive interaction with DNA of daunorubicin (DR), being present in the clinical anti-tumor drug daunoblastina, and the fluorescence probe ethidium bromide (EB) has been studied by parallel-factor analysis (PARAFAC) and full-rank parallel-factor analysis (FRA-PARAFAC) of a fluorescence excitation-emission three-way data array. The PARAFAC algorithm can furnish stable resolution results for the data array studied, if the estimated number of chemical components is consistent with the real number. The FRA-PARAFAC algorithm is not sensitive to the estimated number of components of the fluorescence data array if the estimated number is not less than the real number. Both algorithms gave identical resolution for the three components concerned DR, EB, and the complex EB-DNA. Variations of the equilibrium concentrations of free DR, EB, and the complex EB-DNA were resolved by both algorithms. Experimental observation confirms the hypothesis that DR is an intercalator of DNA and that the binding interactions of DR and EB with DNA are a pair of parallel competitive intercalation reactions on same base sites of DNA. The method exemplified by this study provides a useful approach for studying competitive interactions of different drugs with DNA in the presence of interferents.

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Effects of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (NSC-407347), An alkylating agent derived from 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388)

Cited by 19 publications

References 15 publications

Reduction of 1,3-Diphenyl-1-triazene by Rat Hepatic Microsomes, by Cecal Microflora, and in Rats Generates the Phenyl Radical Metabolite: An ESR Spin-Trapping Investigation

Reduction of 1,3-Diphenyl-1-triazene by Rat Hepatic Microsomes, by Cecal Microflora, and in Rats Generates the Phenyl Radical Metabolite: An ESR Spin-Trapping Investigation

Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates

Competitive interaction of the antitumor drug daunorubicin and the fluorescence probe ethidium bromide with DNA as studied by resolving trilinear fluorescence data: the use of PARAFAC and its modification

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