Details
| Original language | English |
|---|---|
| Pages (from-to) | 164-170 |
| Number of pages | 7 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 112 |
| Publication status | Published - 13 Apr 2016 |
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.
Keywords
- Cancer, Cytostatic, Diterpene, Inhibitor, Kinesin spindle protein, Monoaster
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
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In: European Journal of Medicinal Chemistry, Vol. 112, 13.04.2016, p. 164-170.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function
AU - Pfeffer, Tobias J.
AU - Sasse, Florenz
AU - Schmidt, Christoph F.
AU - Lakämper, Stefan
AU - Kirschning, Andreas
AU - Scholz, Tim
PY - 2016/4/13
Y1 - 2016/4/13
N2 - 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.
AB - 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.
KW - Cancer
KW - Cytostatic
KW - Diterpene
KW - Inhibitor
KW - Kinesin spindle protein
KW - Monoaster
UR - http://www.scopus.com/inward/record.url?scp=84958540695&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2016.02.022
DO - 10.1016/j.ejmech.2016.02.022
M3 - Article
C2 - 26896705
AN - SCOPUS:84958540695
VL - 112
SP - 164
EP - 170
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -