Synthesis and tubulin-binding properties of new allocolchicinoids.
Allocolchicinoids with B- and C-ring variations were synthesized using sequential enyne-metathesis/ Diels-Alder reactions (A-->AB-->ABC approach) and evaluated for their inhibitory effect on tubulin assembly in vitro. (-)-Allocolchicine 11 with methyl ester at C10 and (+/-)-cyclopropyl allocolchicinoid 32 exhibit similar activity than (-)-colchicine (1), probably derived from a similar flexibility in the biphenyl system. The presence of methyl ester at C10 led to a little loss in potency in comparison with the series with methyl ester at C9. A complete loss of activity was observed for allocolchicine 9 with methyl ester at C11.
Boyer
François-Didier
FD
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France. boyer@versailles.inra.fr
Dubois
Joëlle
J
Thoret
Sylviane
S
Dau
Marie-Elise Tran Huu
ME
Hanna
Issam
I
D000818:Animals; D050256:Antimitotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012756:Sheep; D014404:Tubulin / Q000378:metabolism*
D050256:Antimitotic Agents; D014404:Tubulin; C032782:allocolchicine; D003078:Colchicine