3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity

Hsueh-Yun Lee, Jiann Fong Lee, Sunil Kumar, Yi Wen Wu, Wei-Chun HuangFu, Mei-Jung Lai, Yu-Hsuan Li, Hsiang Ling Huang, Fei Chiao Kuo, Che Jen Hsiao, Chun Chun Cheng, Chia Ron Yang, Jing-Ping Liou

研究成果: 雜誌貢獻文章

9 引文 (Scopus)

摘要

A series of 3-aroylindole hydroxamic acids (10–17) were developed based on the concept of a structural combination of tubulin and histone deacetylase (HDAC) inhibitors. This was accomplished by introducing hydroxamic acid-containing moieties at the N1 position of the tubulin assembly inhibitor, compound 9 (SCB01A, BPR0L075, phase II trial). Most of synthetic compounds produced in this way displayed comparable HDAC inhibitory activity, and four (10, 12–14) of them also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC isoforms. In addition, it exhibits remarkable inhibitory activity against the growth cancer cells in vitro and in vivo (PC3 and RPMI-8226 cells). Notably, it suppresses the growth of multiple myeloma xenografts without leading to the death of teated animals like reference compound. In sum, this study provided potential compounds with safer profiles for cancer treatment.
原文英語
頁(從 - 到)1268-1278
頁數11
期刊European Journal of Medicinal Chemistry
125
DOIs
出版狀態已發佈 - 一月 5 2017

指紋

Histone Deacetylases
Tubulin
Bioactivity
Hydroxamic Acids
Tubulin Modulators
Histone Deacetylase Inhibitors
Growth
Multiple Myeloma
Heterografts
Oncology
Neoplasms
Protein Isoforms
Animals
Cells

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

引用此文

3-Aroylindoles display antitumor activity in vitro and in vivo : Effects of N1-substituents on biological activity. / Lee, Hsueh-Yun; Lee, Jiann Fong; Kumar, Sunil; Wu, Yi Wen; HuangFu, Wei-Chun; Lai, Mei-Jung; Li, Yu-Hsuan; Huang, Hsiang Ling; Kuo, Fei Chiao; Hsiao, Che Jen; Cheng, Chun Chun; Yang, Chia Ron; Liou, Jing-Ping.

於: European Journal of Medicinal Chemistry, 卷 125, 05.01.2017, p. 1268-1278.

研究成果: 雜誌貢獻文章

Lee, Hsueh-Yun ; Lee, Jiann Fong ; Kumar, Sunil ; Wu, Yi Wen ; HuangFu, Wei-Chun ; Lai, Mei-Jung ; Li, Yu-Hsuan ; Huang, Hsiang Ling ; Kuo, Fei Chiao ; Hsiao, Che Jen ; Cheng, Chun Chun ; Yang, Chia Ron ; Liou, Jing-Ping. / 3-Aroylindoles display antitumor activity in vitro and in vivo : Effects of N1-substituents on biological activity. 於: European Journal of Medicinal Chemistry. 2017 ; 卷 125. 頁 1268-1278.
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abstract = "A series of 3-aroylindole hydroxamic acids (10–17) were developed based on the concept of a structural combination of tubulin and histone deacetylase (HDAC) inhibitors. This was accomplished by introducing hydroxamic acid-containing moieties at the N1 position of the tubulin assembly inhibitor, compound 9 (SCB01A, BPR0L075, phase II trial). Most of synthetic compounds produced in this way displayed comparable HDAC inhibitory activity, and four (10, 12–14) of them also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC isoforms. In addition, it exhibits remarkable inhibitory activity against the growth cancer cells in vitro and in vivo (PC3 and RPMI-8226 cells). Notably, it suppresses the growth of multiple myeloma xenografts without leading to the death of teated animals like reference compound. In sum, this study provided potential compounds with safer profiles for cancer treatment.",
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AU - Hsiao, Che Jen

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