Showing papers on "Theobromine published in 1979"
TL;DR: The decrease in cellular NAD level produced by y-radiation and by N-methyl-N-nitrosourea is proposed to be caused by an increased flux through poly(ADP-ribose) mediated by anincreased activity of poly( ADP- ribose) polymerase, which consequently lowers the cellular NADlevel.
Abstract: Both N-methylN-nitrosourea and γ-radiation lower cellular NAD in mouse leukaemia cells (L-1210) in a dose-dependent way. The minimum NAD level is reached 2 h after a brief exposure to N-methyl-N-nitrosourea, but within 15 min of y-irradiation. The cells remain metabolically active; they are able to recover their control NAD levels and are impermeable to trypan blue.
Several inhibitors of poly(ADP-ribose) polymerase inhibit the drop in cellular NAD caused by these two agents: 2 mM 5-methylnicotinamide, 1 mM theophylline or 1 mM theobromine inhibit the effect of N-methyl-N-nitrosourea on cellular NAD level; 200 uM thymidine, 500 uM 5-methyl-nicotinamide, 500 αM theophylline and 500 αM theobromine prevent the lowering of cellular NAD by y-irradiation. The extent to which the drop in cellular NAD is inhibited is dependent on both the concentration of cytotoxic agent and of polymerase inhibitor. Caffeine will inhibit the drop in NAD but only at 10 mM, while nicotonic acid is ineffective even at this dose.
The activity of poly(ADP-ribose) polymerase in permeabilized cells immediately after y-radiation increases with dose up to 12 krad, giving a maximal 3.4-fold stimulation of the enzyme activity, whereas the degradation of NAD under conditions optimal for NAD glycohydrolase does not change. The activity of the polymerase shows a close temporal correlation with the NAD drop following both γ-radiation and N-methyl-N-nitrosourea. The enzyme activity is maximal when the NAD content is decreasing at the highest rate and has returned to normal levels when it ceases falling.
In permeabilized cells we can distinguish poly(ADP-ribose) polymerase and NAD glycohydrolase activity by their differential response to inhibitors. The polymerase is sensitive to 5-methylnicotin-amide, theophylline, theobromine and thymidine; the NAD glycohydrolase is sensitive to 5-methyl-nicotinamide and theophylline, but not to theobromine and thymidine.
We propose that the decrease in cellular NAD level produced by y-radiation and by N-methyl-N-nitrosourea is caused by an increased flux through poly(ADP-ribose) mediated by an increased activity of poly(ADP-ribose) polymerase. This consequently lowers the cellular NAD level. This hypothesis implies an involvement of (ADP-ribose)n in the cellular response to cytotoxic drugs.
269 citations
TL;DR: Data are presented which show that the xanthine stimulants caffeine, theophylline, and theobromine as well as the central nervous system convulsant pentylenetetrazol all competitively inhibit [ 3 H] diazepam binding.
189 citations
TL;DR: The incorporation of radioactivity from L -[ 14 CH 3 ]-methionine into coffee by coffee fruits was enhanced by adding theobromine and paraxanthine but was reduced by additions of theophylline and caffeine as discussed by the authors.
52 citations
TL;DR: Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome in opiate-naive rats, five were effective in a dose-related way and their potencies in inducing a QMWS correlated significantly with those in inhibiting low Km cyclic AMP phosphodiesters of rat brain homogenate.
36 citations
36 citations
TL;DR: The prominent effects of increasing concentrations of dietary theobromine were anorexia, decreases in body weight in mature rats, growth retardation in immature rats and atrophy of the thymus glands in rats of both sexes and testicular atrophy in males.
32 citations
TL;DR: In this paper, a rapid method for simultaneous determination of caffeine and theophylline from the serum, saliva, or spinal fluid of neonates was developed, which was performed in less than 10 minutes.
Abstract: A rapid method for simultaneous determination of caffeine and theophylline from the serum, saliva, or spinal fluid of neonates was developed. Fifty-microUter samples were extracted and analyzed by high-pressure liquid chromatography (HPLC) at a low accurately detectable limit of 0.1 mglUter. The sample preparation time was about 40 minutes. Instrumental analysis was performed in less than 10 minutes. Extraction efficiency from repeated analyses was determined to be 95 A precolumn was used to Increase the life of the analytical column. The EMIT-aad| method was compared to HPLC analysis and found to be less efficient.
20 citations
TL;DR: Theobromine was formed only when the cells were incubated with 7-methyl-xanthosine and a methyl donor, methionine, suggesting that part of the biosynthetic route to theobromines synthesis is still functional in the tissue culture.
Abstract: SUMMARY A synthetic medium was developed for the routine subculture of callus and cell suspensions of cocoa. All growth hormones and the coconut milk (CM) supplement of previous media were replaced by indole butyric acid (IBA) and zeatin, at concentrations of 1 mg 1-1 IBA and 005 mg 1-1 zeatin for callus and 10 mg 1-1 IBA and 0-5 mg 1-1 zeatin for cell suspension cultures. During the exponential phase of the growth cycle on this medium, the total phenolics in the callus and cell suspensions declined but then increased at onset of the stationary phase and finally declined again with cell senescence. The flavonoid compositions of the callus and cell suspension were similar and much less varied than that of the original intact cotyledon. Both tissue cultures contained epicatechin, leucocyanidins, caffeic and coumaric acids, all of which are thought to act as flavour precursors when in the intact fermented cotyledon. The methylated purines, theobromine and caffeine, could not be detected in the tissue cultures even in the presence of high nitrate levels in the medium. When precursors of theobromine synthesis such as xanthine, hypoxanthine and 7-methyl-xanthosine, were fed to the cells, theobromine was formed only when the cells were incubated with 7-methyl-xanthosine and a methyl donor, methionine, suggesting that part of the biosynthetic route to theobromine synthesis is still functional in the tissue culture.
19 citations
TL;DR: The antitumorigenic effect of caffeine may be related to its ability to inhibit the binding of active metabolites of carcinogens to cellular DNA.
18 citations
TL;DR: In this article, rates of detritiation from the C-8 position of xanthine, xanthosine, and a series of methylated xanthines were measured over a pH range at 85°, in all cases the results can be interpreted in terms of rate-determining hydroxide ion attack on one or more of the different ionised species present in solution.
Abstract: Rates of detritiation from the C-8 position of xanthine, xanthosine, and a series of methylated xanthines (caffeine, theophylline, theobromine, and paraxanthine) have been measured over a pH range at 85°. In all cases the results can be interpreted in terms of rate-determining hydroxide ion attack on one or more of the different ionised species present in solution; the less the degree of methylation the greater the number of ionisable forms and the larger the number of potential mechanisms. In the case of theobromine and paraxanthine three forms (protonated, neutral, and monoanionic) are involved and in the case of xanthosine a further form (dianionic) makes a contribution to the overall rate. The possibility of zwitterionic contributions are also discussed.
5 citations
TL;DR: In this paper, theobromine was prepared by the methylation of commercially available [2-14C] xanthine with dimethyl sulfate, and the yield was 44.5 % of the initially applied radioactivity.
Abstract: [2-14C] theobromine was prepared by the methylation of commercially available [2-14C] xanthine with dimethyl sulfate. The yield was 44.5 % of the initially applied radioactivity.
TL;DR: The inhibition by caffeine of the binding of polycyclic aromatic hydrocarbons (PAH) to DNA may be related to its effect on AHH.
Patent•
17 May 1979
TL;DR: Theobromine of formula I is reacted with an alkali metal compound, e.g. sodium hydride, potassium hydroxide, etc. to form an acid salt of theobromines, which is then reacted with 6-hydroxyl-2-hexanone of formula II: (R is lower alkyl, unsubstituted or substituted phenyl group) to give 1-(5-oxohexyl)theobrome of formula III as mentioned in this paper.
Abstract: PURPOSE:To prepare the title compound usable as a high-purity pharmaceutical in a high yield hygienically, by reacting an alkali metal salt of theobromine with an organic sulfonyl derivative of 6-hydroxy-2-hexanone. CONSTITUTION:Theobromine of formula I is reacted with an alkali metal compound, e.g. sodium hydride, potassium hydroxide, etc. in an aprotic polar solvent, e.g. dimethylformamide, dimethylacetamide, etc. to form an alkali metal salt of theobromine, which is then reacted with an organic sulfonyl derivative of 6-hydroxyl-2- hexanone of formula II: (R is lower alkyl, unsubstituted or substituted phenyl group) to give 1-(5-oxohexyl)theobromine of formula III. USE:Remarkable vasodilator and erythrocyte deformability improving actions with little side effects.
Patent•
06 Jul 1979
TL;DR: In this article, a xanthine derivative of formula I was obtained by reacting an easily available compound of formula II (one of R 4 WR 6 is H and the other two are methyl) with an alkyne derivative of HC≡C(CH 2 ) n X (X is halogen).
Abstract: NEW MATERIAL:A xanthine derivative of formula I [one of R 1 WR 3 is HC≡C(CH 2 ) n -, (n is 2W5), and the other two are methyl]. EXAMPLE: 1-(5'-Hexynyl)theobromine. USE: Intermediate of medicines. It has peripheral vessel dilating activity and erythrocyte deformation promoting activity, low toxicity and high solubilty, and is useful as an intermediate of a pharmaceutically valuable xanthine derivative (e.g. pentoxifylline). PROCESS: The compound of formula I is prepared by reacting an easily available compound of formula II (one of R 4 WR 6 is H and the other two are methyl) with an alkyne derivative of formula HC≡C(CH 2 ) n X (X is halogen, etc.). The compound of formula II is, e.g. theobromine, theophylline, etc. The hydration of the titled compound gives a pharmaceutical agent. COPYRIGHT: (C)1981,JPO&Japio
TL;DR: The inhibitory effect of xanthines and their derivatives on protein metabolism could not be explained by an increased level of cyclic AMP, a decreased secretion of proteins from the liver cells, an inhibition of amino acid transport, an increased degradation of proteins or an effect at the transcription level.
Patent•
09 Apr 1979
TL;DR: Theobromine or its salt is reacted with an acetal or ketal to produce readily 1-substituted theobromines that has vasodilating activity and erythrocyte deformability as mentioned in this paper.
Abstract: PURPOSE:Theobromine or its salt is reacted with an acetal or ketal to produce readily 1-substituted theobromine that has vasodilating activity and erythrocyte deformability. CONSTITUTION:Theobromine of formulaIor its salt is reacted with an acetal or ketal of formula II (R is residue to lower aliphatic acid, organic sulfonyl; n is 2-6) and the resulting product is hydrolyzed with an acid to produce 1-substituted theobromin of formula III, such as 1-(5-oxohexyl) theobromine.
TL;DR: Tritium exchange at C-8 of xanthosine, theobromine, 1-, 3- and 7-methylxanthine in water has been studied.
Patent•
28 Jun 1979
TL;DR: In this article, 1-(3-p-Toluenesulfonyloxypropyl) theobromine of formula I was used to synthesize a vasodilator and a hematocytolytic agent with little side effects.
Abstract: NEW MATERIAL:1-(3-p-Toluenesulfonyloxypropyl) theobromine of formula I. USE:An intermediate for synthesis of medicines, e.g. 1-(5-oxohexyl) theobromine which is a vasodilator and a hematocytolytic agent with little side effects. PROCESS:One mole of a compound of formula II, obtained by reacting 3-bromo- 1-propanol with an alkali metal salt of theobromine, is reacted with 1-5 moles, preferably 1-1.5 moles of a p-toluenesulfonyl halide in the presence of a tertiary amine in an inert solvent to give the compound of formula I.
TL;DR: In this article, it was shown that 3-methyl-4-amino-5-nitrosouracil (1) and 1,3-dimethyl-4amino,5-nithromorphic acid (2) give fourelectron waves of reduction to the corresponding aminouracils.
Abstract: As a result of a study of the polarographic behavior of 3-methyl-4-amino-5-nitrosouracil (1) and 1,3-dimethyl-4-amino-5-nitrosouracil (II) on a dropping mercury electrode it was shown that in acid and synthetic media they give four-electron waves of reduction to the corresponding aminouracils. The limiting current of these waves is of a diffusion type: Its temperature coefficient does not exceed 2% per I~ the dependence of the limiting current on the square root of the height of the mercury column is linear and passes through the origin; the height of the wave is proportional to the concentration, at least up to 10 -2 M. At pH 7.0-11.0, a separation of waves is observed. In view of this, for a quantitative determination of nitrosouracils it is convenient to use buffer solutions with pH < 7.0 or 0.i-I N sodium hydroxide.