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.
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Russell B
0000-0003-4534-3173
RB
Williams
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Steven M
SM
Martin
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Julie A
JA
Lawrence
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Vanessa L
VL
Norman
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Mark
M
O'Neil-Johnson
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Gary R
GR
Eldridge
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Courtney M
CM
Starks
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
C000621255:5-methoxybifidenone; D000970:Antineoplastic Agents; D017705:Lignans; D014404:Tubulin; D050257:Tubulin Modulators; D053148:Caspase 3