Betulin-3, 28-Diphosphate Salt Complexes With Amines and Their Antioxidant Activity

Abstract

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.

Betulin-3,28-diphosphate as a Component of Combination Cytostatic Drugs for the Treatment of Ehrlich Ascites Carcinoma In Vitro and In Vivo Experiments

“…Betulin-3,28-diphosphate was synthesized according to the methods in [ 27 ]. Betulin (6.0 g, 13.56 mmol) was solved in the mixture of 120 mL of dioxane and 7.08 mL of pyridine (81.6 mmol) in a three-neck flask at room temperature.…”

“…Quantum-chemical calculations were provided by HyperChem 8.0, Hypercube Inc, Gainesville, FL, USA (semiempirical method AM1). Size of the void between BDP molecules is 6 Å for dimer and 10 Å for tetramer [ 27 ].…”

Zinc Oxide Nanoparticles Protected with Terpenoids as a Substance in Redox Imbalance Normalization in Burns

“…As a result of this interaction, cavities are formed inside the dimeric or tetrameric structures, which can accommodate small molecules. Figure S6 shows dimeric or tetrameric structures formed by BDP [ 35 ].…”

The Improvement of Betulin-3, 28-Diphosphate Water-Solubility by Complexation With Amines–meglumine and Xymedon

“…Moreover, phytic acid forms different kinds of complexes with amines due to not only proton transfer, but also non-specific covalent binding [34]. Previously we showed that BDP like phytic acid forms salt complexes with amines [35] by proton transfer reaction like phosphoric acid.…”

“…It is possible that such BDP ionization has the nature of the salt complex formation similar to BDP salt complexation with trisamine [35]. The composition of the BDP-trisamine complex was proved using Job's method, and the conditional stability constant equal to 1130 mol•l -1 was calculated [35]. The interaction of BDP with meglumine in a solution was also studied using 31 P-NMR spectra ( fig.…”