Regioselective hydrostannation of diarylalkynes directed by a labile ortho bromine atom: An easy access to stereodefined triarylolefins, hybrids of combretastatin A-4 and isocombretastatin A-4

International audienceA series of triarylolefins bearing the combretastatin A-4 and the isocombretastatin A-4 cores were synthesized and evaluated. The cooperative ortho-effect of a labile bromine atom in the regioselective hydrostannation of unsymmetrical diarylalkynes leading to stereo-defined triarylolefins is presented

Synthesis and anti-tubulin evaluation of chromone-based analogues of combretastatins

International audienc

Synthesis and biological evaluation of a series of tangeretin-derived chalcones.

International audienceA series of chalcones polyoxygenated on the ring A (with pentamethoxy or 2'-hydroxy-3',4',5',6'-tetramethoxy substitution patterns) was synthesized from tangeretin, a natural Citrus flavonoid. These chalcones were evaluated for their antiproliferative, activation of apoptosis, inhibition of tubulin assembly and antileishmanial activities. Comparison with the reference analogous 3',4',5'-trimethoxylated chalcones showed that such peroxygenated substitution patterns on the ring A were less beneficial to these activities

Synthesis and tubulin-binding properties of new allocolchicinoids.

International audienceAllocolchicinoids 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

Design, synthesis and antiproliferative activities of biarylolefins based on polyhydroxylated and carbohydrate scaffolds

International audienc

Synthesis of anti-microtubule biaryls and preliminary evaluation as vascular-disrupting agents.

International audienceA series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki-Miyaura coupling and Br?ed-acid-mediated cyclodehydration as key steps. The vascular-disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of microtubule assembly, antiproliferative activity against cancer cell lines and normal endothelial cells, modification of endothelial cell morphology, and disruption of endothelial cell cords. Two of these compounds showed promising activities in these assays, with profiles similar to that of the reference drug NAC and markedly different from that of colchicine. Altogether, these results show that dibenzoxepines represent promising new leads for the development of more selective vascular-disrupting agents

Synthesis and biological evaluation of C-13′ substituted 7′-homo-anhydrovinblastine derivatives

International audienc