Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agents

Tsung Chih Chen, Jih Hwa Guh, Hui Wen Hsu, Chun Liang Chen, Chia Chung Lee, Chia Lun Wu, Yu Ru Lee, Jing Jer Lin, Dah Shyong Yu, Hsu Shan Huang

Research output: Contribution to journalArticle

Abstract

Several anthrapyrazolone derivatives derived from 7-chloroanthra[1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra[1,9-cd] pyrazol-6(2H)-one have been prepared by the addition or substitution nucleophilic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1-6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI50, TGI and LC50, respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI50 of 10.498μM and 4.542μM over 60 cell lines which is better than the average GI50 (20.3μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range.

Original languageEnglish
JournalArabian Journal of Chemistry
DOIs
Publication statusPublished - 2015

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Scaffolds
Antineoplastic Agents
Cells
Derivatives
losoxantrone
Telomerase
Assays
Substitution reactions
anthra(1,9-cd)pyrazol-6(2H)-one

Keywords

  • Anthrapyrazolone
  • Antiproliferation
  • Cytotoxicity
  • NCI 60-cell panel assay
  • SRB assay
  • TRAP assay

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agents. / Chen, Tsung Chih; Guh, Jih Hwa; Hsu, Hui Wen; Chen, Chun Liang; Lee, Chia Chung; Wu, Chia Lun; Lee, Yu Ru; Lin, Jing Jer; Yu, Dah Shyong; Huang, Hsu Shan.

In: Arabian Journal of Chemistry, 2015.

Research output: Contribution to journalArticle

Chen, Tsung Chih ; Guh, Jih Hwa ; Hsu, Hui Wen ; Chen, Chun Liang ; Lee, Chia Chung ; Wu, Chia Lun ; Lee, Yu Ru ; Lin, Jing Jer ; Yu, Dah Shyong ; Huang, Hsu Shan. / Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agents. In: Arabian Journal of Chemistry. 2015.
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abstract = "Several anthrapyrazolone derivatives derived from 7-chloroanthra[1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra[1,9-cd] pyrazol-6(2H)-one have been prepared by the addition or substitution nucleophilic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1-6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI50, TGI and LC50, respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI50 of 10.498μM and 4.542μM over 60 cell lines which is better than the average GI50 (20.3μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range.",
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author = "Chen, {Tsung Chih} and Guh, {Jih Hwa} and Hsu, {Hui Wen} and Chen, {Chun Liang} and Lee, {Chia Chung} and Wu, {Chia Lun} and Lee, {Yu Ru} and Lin, {Jing Jer} and Yu, {Dah Shyong} and Huang, {Hsu Shan}",
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AU - Chen, Tsung Chih

AU - Guh, Jih Hwa

AU - Hsu, Hui Wen

AU - Chen, Chun Liang

AU - Lee, Chia Chung

AU - Wu, Chia Lun

AU - Lee, Yu Ru

AU - Lin, Jing Jer

AU - Yu, Dah Shyong

AU - Huang, Hsu Shan

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AB - Several anthrapyrazolone derivatives derived from 7-chloroanthra[1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra[1,9-cd] pyrazol-6(2H)-one have been prepared by the addition or substitution nucleophilic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1-6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI50, TGI and LC50, respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI50 of 10.498μM and 4.542μM over 60 cell lines which is better than the average GI50 (20.3μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range.

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KW - NCI 60-cell panel assay

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KW - TRAP assay

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