New anticancer agents by multicomponent reaction.
The bioactive compounds betulinic acid, fusidic acid and cholic acid are currently the subject of intensive research due to their cytotoxic activity. In a project with MLU and Merseburg University of Applied Sciences, IPB chemists conjugated these active compounds for the first time with the nitroxide compound TEMPO (2,2,6,6-tetramethylpiperidinyloxyl). Using an Ugi multicomponent reaction (U-4CR), they created a substance library from which promising derivatives with increased cytotoxic activity were expected to be fished. Indeed, among the nitroxide-labeled betulin and fusidic acid derivatives, some compounds were found to have potent cytotoxic effects on prostate and colon cancer cell lines. Mode of action studies of the conjugates showed a significant increase in caspase levels in the malignant cells. This suggests the induction of programmed cell death through activation of the caspase cascade. TEMPO, as a stable organic radical with an unpaired electron, can also be used as a spin probe. Thus, the generated conjugates can be detected and analyzed by electron spin resonance (ESR) spectroscopy.
Nitroxide-modified natural products have previously been shown to be useful side-effectors in cancer therapy. As potent antioxidants, they can remove superoxide anions and scavenge carbon-centered radicals. Reactive oxygen species damage cell structures and play a role in tumor development and growth. Antioxidant therapies are increasingly being used to selectively inhibit the proliferation of cancer cells.
