Design, synthesis and biological evaluation of tetracyclic azafluorenone derivatives with topoisomerase I inhibitory properties as potential anticancer agents

Tsung Chih Chen, Dah-Shyong Yu, Shiag-Jiun Chen, Chun-Liang Chen, Chia-Chung Lee, Ying-Yu Hsieh, Lien-Cheng Chang, Jih-Hwa Guh, Jing-Jer Lin, H.-S. Huang

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Abstract

Several 9-chloro-11H-indeno[1,2-c]quinolin-11-one derivatives have been designed which is replacing side chains with different groups containing oxygen, nitrogen or sulfur atoms. Substitution of C-6 on the starting structure, 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one, using apposite nucleophilic group with a suitable base or acid could be obtained 28 novel tetracyclic azafluorenone derivatives. The cytotoxic activity of these analogues was examined in cancer cell lines by MTT assay and compounds 4, 5, 13, and 26 were selected to evaluate in topoisomerase I drug screening assay, respectively. At the same time, 17 compounds were selected for NCI-60 anticancer drug screen to prevent the narrower concept of an in vitro screening model. Its worth to find that 9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (12) showed greater cytotoxicity than another azafluorenone derivatives with an average GI50 of 10.498μM over 60 cell lines. We also found that another analogue, 9-chloro-6-(2-methylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (13), exhibited preferential growth inhibition effect toward cancer cell lines and showed a significant inhibitory effect on topoisomerase I. © 2016.
Original languageEnglish
JournalArabian Journal of Chemistry
DOIs
Publication statusPublished - 2016

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Type I DNA Topoisomerase
Antineoplastic Agents
Cells
Derivatives
Assays
Screening
Cytotoxicity
Sulfur
Pharmaceutical Preparations
Substitution reactions
Nitrogen
Oxygen
Atoms
Acids

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Design, synthesis and biological evaluation of tetracyclic azafluorenone derivatives with topoisomerase I inhibitory properties as potential anticancer agents. / Chen, Tsung Chih; Yu, Dah-Shyong; Chen, Shiag-Jiun; Chen, Chun-Liang; Lee, Chia-Chung; Hsieh, Ying-Yu; Chang, Lien-Cheng ; Guh, Jih-Hwa; Lin, Jing-Jer; Huang, H.-S.

In: Arabian Journal of Chemistry, 2016.

Research output: Contribution to journalArticle

Chen, Tsung Chih ; Yu, Dah-Shyong ; Chen, Shiag-Jiun ; Chen, Chun-Liang ; Lee, Chia-Chung ; Hsieh, Ying-Yu ; Chang, Lien-Cheng ; Guh, Jih-Hwa ; Lin, Jing-Jer ; Huang, H.-S. / Design, synthesis and biological evaluation of tetracyclic azafluorenone derivatives with topoisomerase I inhibitory properties as potential anticancer agents. In: Arabian Journal of Chemistry. 2016.
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abstract = "Several 9-chloro-11H-indeno[1,2-c]quinolin-11-one derivatives have been designed which is replacing side chains with different groups containing oxygen, nitrogen or sulfur atoms. Substitution of C-6 on the starting structure, 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one, using apposite nucleophilic group with a suitable base or acid could be obtained 28 novel tetracyclic azafluorenone derivatives. The cytotoxic activity of these analogues was examined in cancer cell lines by MTT assay and compounds 4, 5, 13, and 26 were selected to evaluate in topoisomerase I drug screening assay, respectively. At the same time, 17 compounds were selected for NCI-60 anticancer drug screen to prevent the narrower concept of an in vitro screening model. Its worth to find that 9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (12) showed greater cytotoxicity than another azafluorenone derivatives with an average GI50 of 10.498μM over 60 cell lines. We also found that another analogue, 9-chloro-6-(2-methylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (13), exhibited preferential growth inhibition effect toward cancer cell lines and showed a significant inhibitory effect on topoisomerase I. {\circledC} 2016.",
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AU - Chen, Shiag-Jiun

AU - Chen, Chun-Liang

AU - Lee, Chia-Chung

AU - Hsieh, Ying-Yu

AU - Chang, Lien-Cheng

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AU - Huang, H.-S.

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