Derivatives of XXXX : synthetic antimitotic agents which interact with plant and mammalian tubulin at a new drug-binding site.

@entity3007 @entity137 @entity73165 @entity14217 @entity19 @entity3878 @entity51385 @entity7575 @entity15060 @entity1778 @entity2862 @entity952 @entity3812 @entity291 @entity5713 @entity17204
A series of derivatives of @entity73165 ( @entity14217 ) was examined for interactions with @entity291 brain tubulin following the demonstration that many members of the class caused significant mitotic effects in intact animals, while others had activity against @entity19 @entity19 @entity1778 . In L1210 cells several @entity14217 derivatives caused a rise in the mitotic index which correlated well with the @entity137 of the drugs. Active @entity14217 derivatives markedly stimulated tubulin-dependent @entity3007 hydrolysis and inhibited tubulin polymerization or induced tubulin oligomer formation, depending on specific reaction conditions. These new agents, however, did not interfere with the binding to tubulin of radiolabeled @entity3812 , @entity5713 , @entity17204 , or @entity3007 . They thus appear to bind at a previously undescribed site on the tubulin molecule. Some @entity14217 derivatives have significant herbicidal activity, causing @entity952 and a rise in the mitotic index in seedling root tissues. Although the @entity14217 derivatives most toxic to plant tissues differ from those most active in inhibiting @entity291 brain tubulin polymerization, virtually all active compounds bear a @entity7575 substituent at position 4 of the @entity51385 ring. Most active derivatives also bear substituents of varying structure at position 2 of this ring, but no clear structure-function pattern is apparent at this position. The @entity15060 rings in the most active herbicidal @entity14217 derivatives either are unsubstituted or bear @entity2862 atoms. Derivatives with @entity3878 substituents have no detectable herbicidal activity. In contrast, interactions with @entity291 brain tubulin are substantially enhanced if the @entity15060 rings bear @entity3878 substituents.
