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The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function.

Publication ,  Journal Article
Pfeffer, TJ; Sasse, F; Schmidt, CF; Lakämper, S; Kirschning, A; Scholz, T
Published in: European journal of medicinal chemistry
April 2016

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.

Duke Scholars

Published In

European journal of medicinal chemistry

DOI

EISSN

1768-3254

ISSN

0223-5234

Publication Date

April 2016

Volume

112

Start / End Page

164 / 170

Related Subject Headings

  • Stereoisomerism
  • Models, Molecular
  • Mitosis
  • Microtubules
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Macrocyclic Compounds
  • Kinesins
  • Humans
  • Euphorbiaceae
 

Citation

APA
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ICMJE
MLA
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Pfeffer, T. J., Sasse, F., Schmidt, C. F., Lakämper, S., Kirschning, A., & Scholz, T. (2016). The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function. European Journal of Medicinal Chemistry, 112, 164–170. https://doi.org/10.1016/j.ejmech.2016.02.022
Pfeffer, Tobias J., Florenz Sasse, Christoph F. Schmidt, Stefan Lakämper, Andreas Kirschning, and Tim Scholz. “The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function.European Journal of Medicinal Chemistry 112 (April 2016): 164–70. https://doi.org/10.1016/j.ejmech.2016.02.022.
Pfeffer TJ, Sasse F, Schmidt CF, Lakämper S, Kirschning A, Scholz T. The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function. European journal of medicinal chemistry. 2016 Apr;112:164–70.
Pfeffer, Tobias J., et al. “The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function.European Journal of Medicinal Chemistry, vol. 112, Apr. 2016, pp. 164–70. Epmc, doi:10.1016/j.ejmech.2016.02.022.
Pfeffer TJ, Sasse F, Schmidt CF, Lakämper S, Kirschning A, Scholz T. The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function. European journal of medicinal chemistry. 2016 Apr;112:164–170.
Journal cover image

Published In

European journal of medicinal chemistry

DOI

EISSN

1768-3254

ISSN

0223-5234

Publication Date

April 2016

Volume

112

Start / End Page

164 / 170

Related Subject Headings

  • Stereoisomerism
  • Models, Molecular
  • Mitosis
  • Microtubules
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Macrocyclic Compounds
  • Kinesins
  • Humans
  • Euphorbiaceae