Preparation and Antitumor Activity of Betulin Dipropionate and its Composites

Betulin dipropionate is a natural compound with high cytotoxicity toward many cancer cells. The one-step synthesis directly from the birch bark without a separate betulin isolation stage was developed to obtain betulin dipropionate. Due to its composition, betulin dipropionate is a promising drug for treating a wide range of diseases. However, the poor water solubility of this compound has limited its applications. We prepared the composites of betulin dipropionate using two methods: ball milling of the mixtures of betulin dipropionate with synthetic and natural polymers, such as polyvinylpyrrolidone polyethylene glycol, fumed silica, arabinogalactan, and preparation of thin films with arabinogalactan by evaporating the aqueous solutions. These composites showed higher water solubility and improved antitumor properties against ascites carcinoma cells and human lung adenocarcinoma cells compared with the initial substance. Furthermore, the cell viability studies based on Annexin V and Propidium iodide probes confirmed the high proapoptotic effect of betulin dipropionate against cancer cells.

OPTIMIZATION OF THE PROCESS OF BIOLOGICALLY – ACTIVE BETULIN DIPROPIONATE PRODUCTION FROM OUTER BIRCH BARK

The aim of this work was the mathematical modeling and selection of optimal regimes for the process of biologically active betulin dipropionate production based on the treatment of birch bark by propionic acid. In order to achieve this aim, two variable factors of the process were varied: X1 – the average size of bark particles (3.5 and 15.0 mm); X2 – the duration of the process. The output parameters were: Y1 – product yield (as a percentage by mass of the absolutely dry bark); Y2 – mass fraction of betulin dipropionate in the product (in percent); Y3 – the yield of betulin dipropionate as a percentage by mass of the absolutely dry bark. For mathematical processing of the results, the Statgraphics Centurion XVI package, the DOE block, the Multi-Factor Categorical procedure were used. It was established by experimental and computational methods that the optimal conditions for obtaining the product with the highest content of betulin dipropionate are as follows: a ratio liquid/solid of 20, an average size of bark particles of 3.5 mm, a time of 8–12 hours. The structure of betulin dipropionate, obtained under optimal conditions, was confirmed by physicochemical methods, the purity of the product was 95%. Due to its low toxicity and valuable pharmacological properties the betulin dipropionate has prospects for use in medicine.