The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function
| Autor: | Tim Scholz, Andreas Kirschning, Tobias J. Pfeffer, Stefan Lakämper, Florenz Sasse, Christoph F. Schmidt |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Macrocyclic Compounds Kinesins Mitosis Microtubules Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Microtubule Cell Line Tumor Drug Discovery Animals Humans Cell Proliferation Pharmacology Natural product Cell growth Organic Chemistry Euphorbiaceae Stereoisomerism General Medicine In vitro 030104 developmental biology chemistry Biochemistry 030220 oncology & carcinogenesis Kinesin Diterpenes Enantiomer Multipolar spindles |
| Zdroj: | European Journal of Medicinal Chemistry. 112:164-170 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.02.022 |
| Popis: | Tonantzitlolone A, a diterpene isolated from the Mexican plant Stillingia sanguinolenta, shows cytostatic activity. Both the natural product tonantzitlolone A and its synthetic enantiomer induce monoastral spindle formation in cell experiments which indicates inhibitory activity on kinesin-5 mitotic motor molecules. These inhibitory effects on kinesin-5 could be verified in in vitro single-molecule motility assays, where both tonantzitlolones interfered with kinesin-5 binding to its cellular interaction partner microtubules in a concentration-dependent manner, yet with a larger effect of the synthetic enantiomer. In contrast to kinesin-5 inhibition, both tonantzitlolone A enantiomers did not affect conventional kinesin-1 function; hence tonantzitlolones are not unspecific kinesin inhibitors. The observed stronger inhibitory effect of the synthetic enantiomer demonstrates the possibility to enhance the overall moderate anti-proliferative effect of the lead compound tonantzitlolon A by chemical modification. |
| Databáze: | OpenAIRE |
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