The Biological Activity of the Novel Vinca Alkaloids 4-chlorochablastine und 4-chlorochacristine
[ Vol. 18 , Issue. ]
Gracia Montag, Helga Stopper, Quoc Anh Ngo and Henning Hintzsche*Pages 1-9 (9)
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 sideeffects including neurotoxicity and bone marrow depression. Therefore, it is very important to develop novel vinca alkaloids with similar efficacy but lower toxicity. 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. 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. 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 Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, CauGiay, Hanoi, Bavarian Health and Food Safety Authority, Eggenreuther Weg 43, 91058 Erlangen
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