Objective: Studies of composition, stability and antioxidant properties of the betulin-3, 28-diphosphate complexes with dopamine and trisamine. Methods:The betulin-3, 28-diphosphate (BDP) interaction with amines in a water-alcohol medium was studied by using spectral methods and potentiometric titration. Biochemical indexes such as catalase, superoxide dismutase (SOD), lactate dehydrogenase (LDH) activities and malondialdehyde (MDA) level were estimated in experiments on rats.Results: BDP was synthesized using betulin by POCl3 treatment in the presence of pyridine in dioxane. The complexation of BDP with amines was confirmed by the 31 P-NMR and FTIR-spectral data. The stoichiometry of BDP-dopamine complexes was equal to 2:1 and 4:1 and its complexes with trisamine were produced in the ratio 1:1 in a water-alcohol medium. The conditional stability constant К′st of the BDP-trisamine complex is 1130±55 mol•l -1 . BDP-Tris complex improved SOD activity up to 30% and up to 105% in the presence of cytostatic-hydrazine sulfate. The MDA level in erythrocytes decreased up to 57% and in combination with cytostatics (5-fluorouracil and hydrazine sulfate)-up to 11-14%. The catalase activity increased by 44-94% and MDA level in erythrocytes decreased by 22-53% under the action BDP-DA complexes that depends on the dose. Conclusion:The BDP forms stable complexes with trisamine and dopamine that make it possible to use this compound as a component of drug delivery system for high toxicity cytostatics and for readily oxidized catecholamines. It has been shown that both its complexes with amines and the combination with cytostatics enhanced antioxidant activity in an experiment in vitro.
Using compression and wetting isotherm analysis, it was shown that lupane triterpenes (betuli nol, betulinol diacetate, betulinic acid) change crucially the state of monolayers and films of C 60 fullerene, nitroxide malonate C 60 methanofullerene, and lecithin and also the films of their mixtures at the water-air interface. The structuring action of triterpenes in the presence of lecithin and C 60 fullerene at high triterpene contents in the film gives rise to uniaxially oriented films similar to thin films of triterpenes (atomic force microscopy data). The formation of mixed bis nitroxide malonate methanofullerene-triterpene films with excess of the latter affords structures shaped like crater like bowls.The lupane triterpenes possess valuable biological prop erties including antitumor, anti HIV 1, antibacterial, an tiinflammatory, and hepatoprotector activities. 1-5 As re gards their chemical nature and the hydrophilic lipophilic balance, triterpenes, for example, betulinol (1), betulinol diacetate (2), and betulinic acid (3), are close to another class of polycyclic saturated hydrocarbons, lipophilic ste rols (such as cholesterol).R 1 = OH, R 2 = CH 2 OH (1); R 1 = OAc, R 2 = CH 2 OAc (2); R 1 = OH, R 2 = COOH (3) The role of lipophilic triterpenes is most often a de crease in the attraction forces between the lipid hydrocar bon chain, thus inducing cooperative interactions in the membrane and finally controlling its fluidity. 6 The stabilization mechanism of biomembranes by triterpenes is based on aggregation, structurization, and clusteriza tion in the systems triterpene-lipophilic physiologically active compounds.The effect of lipophilic physiologically active com pounds was studied in relation to C 60 fullerene, bis ni troxide malonate C 60 methanofullerene (4), and leci thin. Currently C 60 fullerene and its derivatives are known as components of pharmaceutical drugs with a broad spectrum of physiological action. 7,8 The high lipophilicity of fullerene fragment allows the complex es and aggregates formed to penetrate into almost all tissues including the brain. High lipophilicity of fullerene derivatives and their aggregation complexes with physiologically active substances determines, in particu lar, the membranotropic mechanism of their antiviral action. 7
Bis-nitroxide malonate methanofullerene (NO)2-MF was studied as a biomimetic model of reduction-oxidation activity with natural compounds-cytochrome c (cyt c), dihydroquercetin (DHQ), ascorbic acid (AA) and synthetic drug-1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine (xymedon(®)). (NO)2-MF may be used as the component of Langmuir monolayers on an aqueous subphase and as the adsorbate on silica gel. The activity of (NO)2-MF in the reaction with cyt c was compared with the effect of nitroxide species such as gaseous nitric oxide, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) by using UV-vis and EPR-spectra. It has been shown, that iron(III) in cyt c(3+) under action (NO)2-MF was reduced up to iron(II), similar effect was observed under the influence of gaseous NO in aqueous solution, but reduction of iron(III) in heme cyt c was reversible in the presence of TEMPO. Therefore, the state of Fe-heme in cyt c can be used as the indicator of the interaction of cyt c with nitroxide species in vitro. The interaction of cyt c, DHQ, xymedon(®) with (NO)2-MF monolayers was confirmed by the increasing of limiting area А0 from 0.88 nm(2) up to 1.70 nm(2) of (NO)2-MF on the aqueous subphase, by the paramagnetism and UV-vis spectral data changes. These results can be explained by appearance of oxoammonium ion (NO(+))2-MF adlayers and monolayers. The antioxidant and regenerating effects were shown when treating wounds by xymedon(®) in the presence of additives (0.001%) of (NO)2-MF in the experiments on the rats.
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