Cell differentiation enhancement by hydrophilic derivatives of 4,8-dihydrobenzo[1,2-b:5,4-b′]dithiophene-4,8-diones in HL-60 leukemia cells

被引：8

作者：

Wen, Yen-Fang

Lee, Kuo-Hsiung

Huang, Pi-Tsan

Chen, Mei-Hwai

Shin, Wuu-Chian

Huang, Li-Jiau

Hsu, Mei-Hua

Chen, Chun-Jen

Kuo, Sheng-Chu ^{[1
]}

机构：

[1] China Med Univ, Grad Inst Pharmaceut Chem, Taichung, Taiwan

[2] Ind Technol Res Inst, Pharmaceut Technol Div, Biomed Engn Ctr, Sect 2, Hsinchu 31015, Taiwan

[3] Univ N Carolina, Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 10期

关键词：

benzodithiophene; pharmacokinetic; cell differentiation; apoptosis; anti-leukemia;

D O I：

10.1016/j.bmcl.2007.02.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Among five carboxamide derivatives (13-17), N-(2-dimethylaminoethyl)-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione-2-carboxamide (13) showed the greatest enhancement of all-trans retinoid acid (ATRA)-induced differentiation in HL-60 cells, inducing nearly complete differentiation at a concentration of 0.02 mu M. On the other hand, 2-hydroxymethyl-4,8-dihydrobenzo[1,2b:5,4-b']dithiophene-4,8-dione (2) and 2-(1-hydroxylethyl)-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione (18) exhibited excellent and equally potent differentiation effects on HL-60 cells. To improve their water solubility, ester-type hydrophilic prodrugs (23-26) were also synthesized. Compounds 13 and 23-26 are identified in this paper as new anti-leukemic drug candidates. (c) 2007 Published by Elsevier Ltd.

引用

页码：2908 / 2912

页数：5