The interaction with tubulin of a series of stilbenes based on combretastatin A-4.
A series of stilbenes, based on combretastatin A-4, were synthesised. A structure-activity study was carried out to characterise the interaction of these agents with tubulin. The substitution of small alkyl substituents for the 4'-methoxy group of combretastatin A-4 and the loss of the 3'-hydroxyl group does not have a major effect on the interaction with tubulin. trans-Stilbenes were shown to bind tubulin, but do not inhibit microtubule assembly. This work, together with previous studies, has been used to propose an idealised structure for a tubulin-binding agent of this type.
Woods
J A
JA
CRC Department of Experimental Chemotherapy, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Hadfield
J A
JA
Pettit
G R
GR
Fox
B W
BW
McGown
A T
AT
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000633:toxicity; D001667:Binding, Competitive; D002453:Cell Cycle / Q000187:drug effects; D007941:Leukemia P388; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D008940:Mitotic Index / Q000187:drug effects; D015394:Molecular Structure; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014404:Tubulin; C058728:fosbretabulin