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

verfasst von

Tobias J. Pfeffer, Florenz Sasse, Christoph F. Schmidt, Stefan Lakämper, Andreas Kirschning, Tim Scholz

Abstract

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.

Organisationseinheit(en)

Institut für Organische Chemie
Zentrum für Biomolekulare Wirkstoffe (BMWZ)

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Georg-August-Universität Göttingen
ETH Zürich

Typ

Artikel

Journal

European Journal of Medicinal Chemistry

Band

112

Seiten

164-170

Anzahl der Seiten

7

ISSN

0223-5234

Publikationsdatum

13.04.2016

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Pharmakologie, Wirkstoffforschung, Organische Chemie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.ejmech.2016.02.022 (Zugang: Geschlossen)