Lucie Heller

Beta-boswellic acids are triterpenoids being generic to the plants of genus boswellia. Although they were shown to exhibit different biological activities, the cytotoxic potential of b-boswellic acid derivatives remained by and large unexploited. To expand the potential of these compounds we developed simple procedures for the interconversion of the most important b-boswellic acids 1-4 and prepared several other derivatives 5-48. These compounds were screened for their cytotoxic activity in sulforhodamine B assays employing several human tumor cell lines and nonmalignant mouse fibroblasts. One of these compounds, a difluoromethylester of 3-O-acetyl-11-keto-beta-boswellic acid 23, was cytotoxic for human breast adenocarcinoma cells MCF-7 (EC50 = 6.5 mM) while being significantly less cytotoxic for the mouse fibroblasts.

Drotaverine (also known as dihydroperparine or No‐Spa^®) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC₅₀ values as low as 3.0 μM were observed in SRB assays for HT‐29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was observed after 24 h. Extra annexin V‐FITC/PI assays and flow cytometry revealed drotaverine mainly to act as a cytostatic and only to a minor extent as cytotoxic agent.