Background: Vinca alkaloids are important cancer drugs belonging to the class of antimitotic
agents. The most commonly used substances are vinblastine and vincristine, other compounds
are vinorelbine and vinflunine. All of them are very effective drugs but their use is limited by severe
side-effects including neurotoxicity and bone marrow depression. Therefore, it is very important to
develop novel vinca alkaloids with similar efficacy but lower toxicity.
Methods: Here, we analyzed two new compounds, 4-chlorochablastine and 4-chlorochacristine, with
regard to their biological activity. These novel compounds were applied to a leukemia cell line at
clinically relevant concentrations. For comparison, the established vinca alkaloids vinblastine, vincristine,
vinorelbine, and vinflunine were also tested.
Results: Both novel substances decreased cellular proliferation. Apoptosis was found to be increased
using two different methods reflecting early and late apoptosis. Cell cycle analysis revealed a clear
decrease in G1-cells and an increase in G2/M-cells indicating an arrest in mitosis. In general, 4-
chlorochablastine and 4-chlorochacristine caused these effects at concentrations higher than those
needed for vinblastine, vincristine, and vinorelbine, but the potency was approximately in the range
Conclusion: Taken together, the results show first indications that these novel vinca alkaloids might
be effective and that they warrant further analysis.