Design and Evaluation of Betulin-Based Anti-Cancer Compounds

Overview

Betulin is a natural compound present in the bark of birch trees, which are abundant in North America. Betulin has been shown and recognized by the National Cancer Institute as having promising anti-cancer effects. However, there are no betulin-based anti-cancer drugs today due to betulin’s poor solubility in aqueous media like blood serum and lack of effective activity against cancer cell lines in low (nM) concentrations. This project modifies the molecular structure of betulin-derivatives to increase their effectiveness against cancer cells. Betulin was extracted from birch bark by using a series of organic solvents. Betulonic acid was synthesized from betulin by using an oxidation reaction where the primary alcohol group in betulin was replaced by a carboxyl group and the secondary alcohol was replaced by a ketone. Then, the ketone was reduced to a hydroxyl group once again to produce betulinic acid. To improve bioavailability, the molecular structure of betulinic acid was modified to realize different anti-cancer compounds. Specifically, betulinic acid was combined with several different amines to synthesize different analogs. The potency of the three anti-cancer compounds was evaluated in-vitro on cell-lines for prostate cancer. The IC50 values showed that the betulin analogs are effective on cancer cells in the micro-molar concentrations. However, most commercial anti-cancer drugs are effective in nano-molar concentrations. The next steps would be to synthesize betulin-salts from the analogs to further increase solubility, and to add other active agents to the betulin molecule to further improve effectiveness.

Competition history

AJAS 2017 Category not listed

Related projects

ISEF · 2016