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

A series of diversely substituted biarylolefins based on carbohydrate and dihydroxyethylene scaffolds were synthesized and evaluated for antiproliferative activity against a panel of human tumor cell lines. Among the thirty-five yet unknown biarylolefins prepared, six displayed potent antiproliferative activities with IC50 values in the micromolar and submicromolar range. As a new type of antiproliferative agent, the most potent compound 26 showed an IC50 value of 70 nM against SK-OV3 cell line (ovarian cancer). All the synthesized compounds exhibited a poor or modest tubulin polymerization inhibitory activity suggesting another mode of action for these compounds. Molecular docking simulations to the colchicine binding site of tubulin of representative compounds have been used to explain the lack of activity as inhibitors of tubulin polymerization.

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► New biarylolefins are prepared from carbohydrate and dihydroxymethylethylene scaffolds.
► Six of thirty-five new compounds displayed a broad spectrum of antitumor activity.
► The most potent compound had IC50 = 70 nM against SK-OV3 ovarian cancer cell line.