Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives

Chih Hua Tseng, Yeh Long Chen, Pei Jung Lu, Chia Ning Yang, Cherng Chyi Tzeng

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85 Citations (Scopus)

Abstract

Although the quinoline ring is found in a wide variety of biologically active compounds and is frequently condensed with various heterocycles, synthesis and biological evaluation of the indenoquinoline skeleton attracts only very limited attention. We report herein the synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives against the growth of six cancer cell lines including human cervical epithelioid carcinoma (HeLa), oral squamous cell carcinoma (SAS), hepatocellular carcinoma (SKHep), human stomach adenocarcinoma (AGS), prostate cancer (PC-3), and non-small cell lung cancer (A549). The results indicated that 9-methoxy-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (17b) is more active than its C6-amino derivative 17a, C6-morpholine and C6-piperidine isomers, 17c and 17d, respectively. Treatment of 17b with NH2OH afforded its hydroxyimino derivative 20 which is more active than the carbonyl precursor 17b. More potent agents were obtained by further derivatization of 20. Thus, antiproliferative activities decreased in an order of aminoalkoxyimino 22a-d > hydroxyimino 20 > alkoxyimino 21, 22e > carbonyl 17b. Both AGS and A549 were resistant to camptothecin with GI50 values of 23.76 and 2.80 μM, respectively, while GI50 values for 22a-d were in the range of 5.93-7.11 μM and 0.38-0.87 μM, respectively. Among them, 22b was the most potent with GI50 values of 0.52, 0.74, 6.76, and 0.64 μM against the growth of HeLa, SKHep, AGS, and A549 cells, respectively. Flowcytometric analysis indicated 22c can induce cell cycle arrest in S phase, and DNA polyploidy (>4n) followed by apoptosis.

Original languageEnglish
Pages (from-to)3153-3162
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number6
DOIs
Publication statusPublished - 2008 Mar 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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