title: Synthesis and antiproliferative activities of ottelione a analogues.
abstract: Through the syntheses of its C-1 desvinyl, C-7 methylene, C-7 exocyclic ethylidene, and various C-3 phenylmethyl analogues, the structure-activity relationship of antimitotic ottelione A (4) against tubulin and various cancer cells was established. The results indicated that compound 4 was a colchicine-competitive inhibitor and that the C-1 vinyl group is unnecessary for its potency, whereas the C-7 exocyclic double bond is essential, possibly because of its irreversible interaction with tubulin. Further optimization of the substituents on the phenylmethyl group at the C-3 position generated compound 10g with a 3'-fluoro-4'-methoxyphenylmethyl substituent, which was 6-38-fold more active against MCF-7, NCI-H460, and COLO205 cancer cells relative to 4. Results from in vitro tubulin polymerization assay confirmed the potency of compounds 4, 10g, and 11a.
authors.affiliation: Department of Chemistry, National Tsing Hua University , Hsinchu, Taiwan, Republic of China.
authors.forename: Tsai-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Chemistry, National Tsing Hua University , Hsinchu, Taiwan, Republic of China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Tu
authors.affiliation: Development Center for Biotechnology , No. 101, Lane 169, Kangning Street, Xizhi City, Taipei County, Taiwan 221, Republic of China.
authors.forename: Win-Yin
authors.initials: WY
authors.lastname: Wei
authors.affiliation: Development Center for Biotechnology , No. 101, Lane 169, Kangning Street, Xizhi City, Taipei County, Taiwan 221, Republic of China.
authors.forename: Hsiang Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Applied Chemistry, National Chiayi University , No. 300, Syuefu Rd., Chiayi City, Taiwan 60004, Republic of China.
authors.forename: Chih-Shang
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Development Center for Biotechnology , No. 101, Lane 169, Kangning Street, Xizhi City, Taipei County, Taiwan 221, Republic of China.
authors.forename: Ying-Shuan E
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Development Center for Biotechnology , No. 101, Lane 169, Kangning Street, Xizhi City, Taipei County, Taiwan 221, Republic of China ; Department of Applied Chemistry, National Chiayi University , No. 300, Syuefu Rd., Chiayi City, Taiwan 60004, Republic of China.
authors.forename: Jiann-Jyh
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Chemistry, National Tsing Hua University , Hsinchu, Taiwan, Republic of China.
authors.forename: Chin-Kang
authors.initials: CK
authors.lastname: Sha
keywords: anticancer; antimitotic; microtubule; ottelione A; tubulin