Synthesis and Biological Evaluation of Novel Furozan-Based NitricOxide-Releasing Derivatives of 23-Hydroxy Betulinic Acid and 3-oxo-23-hydroxybetulinic acid as Potential Anti-Tumor Agents

To search for novel nitric oxide (NO)-releasing anti-tumor agents, two series of furoxan-based NO-releasing derivatives of 23-Hydroxybetulinic acid and 3-oxo-23-hydroxybetulinic acid were designed and synthesized. The nitrate/nitrite levels in the cell lysates were assayed and the results showed that these derivatives could produce high levels of NO in vitro. Then the antiproliferative activity of these hybrids against four human cancer cell lines was further determined, among which, compound 20a was the most promising derivative with an IC50 under 10 μM on all tested cell lines. The preliminary structure-activity relationships were concluded based on present experimental data.