Isolation and Identification of the Novel Tubulin Polymerization Inhibitor Bifidenone

The pursuit of structurally novel compounds has led to the isolation of a series of neolignans (2–6), for which the structures have been determined from microgram quantities using microcryoprobe NMR technology. Compounds 2–6 provided some unexpectedly clear structure–activity relationship data, with compound 2 demonstrating significantly more potency in the in vitro cytotoxicity assay than the other analogues. Further screening found that compound 2 induces apoptosis with activation of caspase 3/7. The NCI Compare algorithm suggested that compound 2 acts through the inhibition of tubulin/microtubule dynamics. Compound 2 was confirmed to be a tubulin polymerization inhibitor that binds directly to tubulin.