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

Yu Wen Chen, Yeh Long Chen, Chih Hua Tseng, Chih Chung Liang, Chia Ning Yang, Yun Chin Yao, Pei-Jung Lu, Cherng Chyi Tzeng

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4446-4461
Number of pages16
JournalJournal of Medicinal Chemistry
Volume54
Issue number13
DOIs
Publication statusPublished - 2011 Jul 14

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Non-Small Cell Lung Carcinoma
Solubility
Biological Availability
Water
Lung Neoplasms
Quinolines
Growth
Nude Mice
Oral Administration
Neoplasms
Salts
Apoptosis
Lung
quinoline
1-(4-(furo(2,3-b)quinolin-4-ylamino)phenyl)ethanone O-2-aminoethyloxime

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Chen, Yu Wen ; Chen, Yeh Long ; Tseng, Chih Hua ; Liang, Chih Chung ; Yang, Chia Ning ; Yao, Yun Chin ; Lu, Pei-Jung ; Tzeng, Cherng Chyi. / Discovery of 4-anilinofuro[2,3- b ]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 13. pp. 4446-4461.
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Discovery of 4-anilinofuro[2,3- b ]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers. / Chen, Yu Wen; Chen, Yeh Long; Tseng, Chih Hua; Liang, Chih Chung; Yang, Chia Ning; Yao, Yun Chin; Lu, Pei-Jung; Tzeng, Cherng Chyi.

In: Journal of Medicinal Chemistry, Vol. 54, No. 13, 14.07.2011, p. 4446-4461.

Research output: Contribution to journalArticle

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