Synthesis and in vitro antitumor activity of novel naphthyridinone derivatives

详细信息    查看全文

• 作者：Xue-Dong Jia^a ; ^b ; Shuo Wang^a ; Ming-Hua Wang^a ; Ming-Liang Liu^a ; ^{lmllyx@126.com} ; Gui-Min Xia^a ; Xiu-Jun Liu^a ; Yun Chai^a ; Hong-Wei He^a ; ^{hehwei@imb.pumc.edu.cn}
• 关键词：Naphthyridinones ; Synthesis ; Antitumor activity ; Voreloxin
• 刊名：Chinese Chemical Letters
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：28
• 期：2
• 页码：235-239
• 全文大小：353 K
• 卷排序：28

文摘

A series of naphthyridinone derivatives based on 1a (a precursor of Voreloxin) were designed and synthesized. Seven compounds having >70% inhibition against HL60 at 30 μmol/L were further evaluated for their in vitro antitumor activity by SRB assay. Results reveal that thiazol-2-yl and 3-aminomethyl-4-benzyloxyimino-3-methylpyrrolidin-1-yl groups are optimal at the N-1 and C-7 positions of naphthyridinone core, respectively. 10j exhibits broad-spectrum activity (IC50: <0.5–6.25 μmol/L) against all of the tested cell lines including Etoposide- and/or 1a-resistant ones, and is 1.3-fold to >100-fold more potent than the two references against eight of these cell lines.