BETULIN-3, 28-DIPHOSPHATE SALT COMPLEXES WITH AMINES AND THEIR ANTIOXIDANT ACTIVITY

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 POCl 3 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.