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.

Graphical abstractNew allocolchicinoids with B- and C-ring variations were synthesized and evaluated for their inhibitory effect on tubulin assembly.Figure optionsDownload full-size imageDownload as PowerPoint slide