Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents
- 作者：Li-Chen Chou ; Li-Jiau Huang ; Jai-Sing Yang ; Fang-Yu Lee ; Che-Ming Teng ; Sheng-Chu Kuo
- 关键词：Furopyrazole ; YC-1 ; Cell differentiation ; Anti-leukemia agent
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 February 2007
- 卷：15
- 期：4
- 页码：1732-1740
- 文件大小：930 K
摘要
As part of our continuing search for potential anticancer drug candidates in YC-1 analogs, several 1-benzyl-3-(substituted aryl)-5-methylfuro[3,2-c]pyrazoles were synthesized and evaluated for their cytotoxicity against HL-60 cell line. Among these compounds, 1-benzyl-3-(5-hydroxymethyl-2-furyl)-5-methylfuro[3,2-c]pyrazole (1) showed more potency than YC-1. Through investigation of action mechanism, it was found that compound 1 induced terminal differentiation of HL-60 cells toward granulocyte lineage and promoted HL-60 cell differentiation by regulation of Bcl-2 and c-Myc proteins. Meanwhile, compound 1 also demonstrated apoptosis inducing effect. Such anti-leukemia mechanism of action is apparently different from that of YC-1 which mainly works by inducing apoptosis, but not cell differentiation. Therefore, compound 1 is identified here as a new lead compound of cell differentiating agent and apoptosis inducer for further development of new anti-leukemia agents.