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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Pfeffer, TJ; Sasse, F; Schmidt, CF; Lakämper, S; Kirschning, A; Scholz, T

Published Date

  • April 2016

Published In

Volume / Issue

  • 112 /

Start / End Page

  • 164 - 170

PubMed ID

  • 26896705

Electronic International Standard Serial Number (EISSN)

  • 1768-3254

International Standard Serial Number (ISSN)

  • 0223-5234

Digital Object Identifier (DOI)

  • 10.1016/j.ejmech.2016.02.022

Language

  • eng