Structure‐Activity Relationships of Terpendole E and Its Natural Derivatives

Terpendole E (TerE) is the first natural product that inhibits mitotic kinesin Eg5 (kinesin spindle protein). Recently, TerE is suggested to have a different binding site and/or inhibitory mechanism than other L5 loop‐binding type Eg5 inhibitors. Here, we report the structure‐activity relationships...

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Bibliographic Details
Published in:ChemistrySelect (Weinheim) 2017-02, Vol.2 (4), p.1533-1536
Main Authors: Nagumo, Yoko, Motoyama, Takayuki, Hayashi, Toshiaki, Hirota, Hiroshi, Aono, Harumi, Kawatani, Makoto, Osada, Hiroyuki, Usui, Takeo
Format: Article
Language:English
Subjects:
ATPase activity
Eg5
structure-activity relationships
Terpendole E
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Summary:Terpendole E (TerE) is the first natural product that inhibits mitotic kinesin Eg5 (kinesin spindle protein). Recently, TerE is suggested to have a different binding site and/or inhibitory mechanism than other L5 loop‐binding type Eg5 inhibitors. Here, we report the structure‐activity relationships (SARs) of natural TerE derivatives, including two compounds not reported before. Our SAR results indicated that the paspaline‐like indole‐diterpene skeleton is important for Eg5 inhibition, and that both further oxidation except for 11‐position and further prenylation decreases the Eg5 inhibitory activity. Structure‐activity relationship results indicate that the paspaline‐like indole‐diterpene skeleton in terpendole E and its natural derivatives is important for the inhibition of the mitotic kinesin spindle protein Eg5.
ISSN:2365-6549
2365-6549
DOI:10.1002/slct.201602015