Synthesis and antiproliferative evaluation of 9-methoxy-6-(piperazin-1-yl)- 11H-indeno[1,2-c]quinoline-11-one derivatives. Part 4

Chih Hua Tseng, Cherng Chyi Tzeng, Chien Chih Chiu, Chiao Li Yang, Pei Jung Lu, Chon Kit Chou, Chun Yen Liu, Yeh Long Chen

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

We have synthesized certain indeno[1,2-c]quinolin-11-one derivatives for antiproliferative evaluation. Among them, 9-methoxy-6-{4-[(oxiran-2-yl)methyl] piperazin-1-yl}-11H-indeno[1,2-c]quinolin-11-one O-(oxiran-2-yl)methyl oxime (12) exhibited strong antiproliferative activities against the growth of Hela, SKHep, MDA-MB-231, and H1299 cells with IC50 values of 0.54, 0.99, 0.79, and 1.18 μM respectively. Compound 12 was also found to be a potent DNA intercalating agent. Mechanism studies indicated that DNA damage was strongly induced by 12-treated cells even at a low concentration of 5.0 μM. Our results demonstrated that 12 significantly increased Bax expression, activation of caspase-3 and -7, enhanced the cleavage of PARP, and decreased Bcl-2 expression in H1299 cells. Compound 12 also significantly decreased the HDAC6, SIRT1, FOXO3a, p-Akt, and PTEN expression in H1299 cells.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalMedChemComm
Volume5
Issue number7
DOIs
Publication statusPublished - 2014 Jul

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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