Gracia Montag, Helga Stopper, Quoc Anh Ngo and Henning Hintzsche*Pages 222-230 (9)
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 of vinflunine.
Conclusion: Taken together, the results show first indications that these novel vinca alkaloids might be effective and that they warrant further analysis.
Cytotoxicity, HL-60 cells, vinca alkaloids, chlorochablastine, chlorochacristine, vinblastine, vincristine, vinflunine, vinorelbine.
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, CauGiay, Hanoi, Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg