Isolation and Identification of the Novel Tubulin Polymerization Inhibitor Bifidenone.

Autor: Williams RB; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., Martin SM; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., Lawrence JA; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., Norman VL; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., O'Neil-Johnson M; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., Eldridge GR; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States., Starks CM; Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc. , 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2017 Mar 24; Vol. 80 (3), pp. 616-624. Date of Electronic Publication: 2016 Nov 14.
DOI: 10.1021/acs.jnatprod.6b00893
Abstrakt: 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.
Databáze: MEDLINE
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