Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors

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• 作者：Liping Wang^&dagger ; ; Rong Wu^&dagger ; ; Wenwei Fu ; Yuanzhi Lao ; Changwu Zheng ; Hongsheng Tan ; ^{ths97029@163.com" class="auth_mail" title="E-mail the corresponding author} ; Hongxi Xu ; ^{xuhongxi88@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Oblongifolin C ; Modification ; Derivatives ; c-Met kinase inhibitor ; Cytotoxicity ; HCC827 cell line ; Structure&ndash ; activity relationships
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：24
• 期：18
• 页码：4120-4128
• 全文大小：919 K

文摘

Oblongifolin C, one of the polyprenylated benzoylphloroglucinol natural products (PPAPs) isolated from the fruits of Garcinia yunnanensis Hu, was recently discovered to be a potent anti-tumor agent. A collection of 12 derivatives with modifications on the benzophenone moieties were synthesized and tested for c-Met kinase inhibition and cytotoxicity against the HepG2, Miapaca-2, HCC827, Hela, A549, AGS, and HT-29 cell lines in vitro. An oxidized derivative, 10, was found to possess strong inhibition and anti-migration properties in the HCC827 cell line and serves as a potential lead compound for the development of new anticancer drugs. In addition, structure–activity relationships (SAR) were also evaluated to provide key information for future anticancer drug development.