Antitumor Agents 259. Design, Syntheses, and Structure-Activity Relationship Study of Desmosdumotin C Analogs

详细信息    查看全文

• 作者：Kyoko Nakagawa-Goto ; Tzu-Hsuan Chen ; Chieh-Yu Peng ; Kenneth F. Bastow ; Jiu-Hong Wu ; Kuo-Hsiung Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：July 12, 2007
• 年：2007
• 卷：50
• 期：14
• 页码：3354 - 3358
• 全文大小：81K
• 年卷期：v.50,no.14(July 12, 2007)
• ISSN：1520-4804

文摘

Desmosdumotin C (1) and its analogs previously showed potent, selective in vitro anticancer activity. Toexplore structure-activity relationships of 1 and further increase potency and selectivity, 15 novel analogs(7-15 and 21-26) were synthesized and evaluated for cytotoxity against several human tumor cell lines,as well as inhibition of human endothelial (HUVEC) replication. 4-Bromo-3',3',5'-tripropyl analog 26 showedsignificant cytotoxity against A549, A431, 1A9, and HCT-8 with ED₅₀ values of 1.0, 1.2, 0.9, and 1.3g/mL, respectively. Compound 26 also strongly inhibited the growth of matched tumor cells, KB-VIN andits parent cell KB. Furthermore, analogs 13 and 21 were over 5-fold more potent against KB-VIN than KB.Bromination of ring-B and tripropyl functionalization of ring-A enhanced activity, while alkylation of ring-Bpromoted KB-VIN/KB selectivity. 2-Furyl analog 16 showed selective activity against HUVEC, suggestingthat it may have potential as a new prototype for angiogenesis inhibition.