Cucurbitacins are naturally occurring compounds found in many plants of the Cucurbitaceae family. They are of much interest to the medicinal research community due to the recognition of their anticancer and hepatoprotective activities. Cucurbitacins were also known for their potent and differential cytoxicity. Optimizing the anticancer activity in order to produce a less toxic product was always a challenge due the complexity of the cucurbitacin's skeleton. A molecular modeling study in our group has shown the potential for developing novel cucurbitacin derivatives with potent anticancer and low toxicity. The goal of this project is to synthesize cucurbitacin derivatives and study their anticancer effect on cancer cell lines.

Cucurbitacin compounds were isolated and characterized through standard chromatographic (LC and HPLC) and spectroscopic (MS, NMR) techniques. Derivatization of cucurbitacin B, D, E and I were achieved through Williamson Reaction, NaBH₄, Pd/H₂ and acetylation reactions.

Anticancer activities were conducted using HeLa, PC3 and HepG2 cancer cell lines. Cell culture data showed derivatization of cucurbitacins induces a wide range of reduction in cytotoxicity. Cucurbitacin derivatives still demonstrate differential cytotoxicity. Correlation of cytotoxicity and log P was established.