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

doi:10.1039/C4MD00133H

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,^a Cherng-Chyi Tzeng,^b Chien-Chih Chiu,^c Chiao-Li Yang,^b Pei-Jung Lu,^d Chon-Kit Chou,^c Chun-Yen Liu^e and Yeh-Long Chen*^b

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* Corresponding authors

^a School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

^b Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
E-mail: yeloch@kmu.edu.tw
Fax: +886 7 3125339
Tel: +886 7 3121101 ext. 2684

^c Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

^d Institute of Clinical Medicine, National Cheng-Kung University, School of Medicine, 138 Sheng-Li Road, Tainan 704, Taiwan

^e Department of Life, Science National Taiwan Normal University, Taipei 116, Taiwan

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.

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DOI: https://doi.org/10.1039/C4MD00133H
Article type: Concise Article
Submitted: 24 Mar 2014
Accepted: 03 May 2014
First published: 06 May 2014

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Med. Chem. Commun., 2014,5, 937-948

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

C. Tseng, C. Tzeng, C. Chiu, C. Yang, P. Lu, C. Chou, C. Liu and Y. Chen, Med. Chem. Commun., 2014, 5, 937 DOI: 10.1039/C4MD00133H

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

Abstract

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

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