当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of 4-anilinofuro[2,3-b]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers.

Discovery of 4-anilinofuro[2,3-b]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers.

Abstract：

:We have reported the preparation and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinolines. However, drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by these compounds prompted us to search for newer derivatives. Among them, (E)-1-(4-(furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone O-2-aminoethyloxime (13a) is selectively active against the growth of NCI-H460 and is highly water-soluble (63 μg/mL). Its hydrochloride salt, 13a·HCl exhibited not only excellent water solubility (1049 μg/mL) but also a high oral bioavailability (57.1%). Compound 13a may cause cancer cell apoptosis through inducing mitotic arrest and mitotic catastrophe mechanism. Xenographic studies indicated the tumor size with 13a·HCl treated nude mice was significantly lower than control. Further evaluation in an orthotopic lung cancer model indicated that 13a·HCl can be absorbed readily through oral administration, distributed to lung tissue, and exhibited significant efficacy in inhibiting the growth of lung cancers.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chen YW,Chen YL,Tseng CH,Liang CC,Yang CN,Yao YC,Lu PJ,Tzeng CC

doi

10.1021/jm200046z

subject

Has Abstract

pub_date

2011-07-14 00:00:00

pages

4446-61

issue

13

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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