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

Arabian Journal of Chemistry (Dec 2019)

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

Affiliations

Tsung-Chih Chen: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
Jih-Hwa Guh: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan
Hui-Wen Hsu: School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
Chun-Liang Chen: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
Chia-Chung Lee: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
Chia-Lun Wu: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
Yu-Ru Lee: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
Jing-Jer Lin: Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei 100, Taiwan
Dah-Shyong Yu: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital and Institute of Preventive Medicine, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Corresponding authors at: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. Tel.: +886 2 87923100x19390; fax: +886 2 8792 7282 (D.-S. Yu). Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Tel.: +886 2 2736 1661x7525; fax: +886 2 87923169 (H.-S. Huang).
Hsu-Shan Huang: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Corresponding authors at: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. Tel.: +886 2 87923100x19390; fax: +886 2 8792 7282 (D.-S. Yu). Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Tel.: +886 2 2736 1661x7525; fax: +886 2 87923169 (H.-S. Huang).

Journal volume & issue: Vol. 12, no. 8
pp. 2864 – 2881

Abstract

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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 10.498 μM and 4.542 μM over 60 cell lines which is better than the average GI50 (20.3 μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range. Keywords: Anthrapyrazolone, SRB assay, TRAP assay, Cytotoxicity, NCI 60-cell panel assay, Antiproliferation

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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