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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1268-1278
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume125
DOIs
Publication statusPublished - Jan 5 2017

Fingerprint

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

Keywords

  • 3-Aroylindoles
  • Anticancer agents
  • Histone deacetylase inhibitors
  • Tubulin polymerization inhibition

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

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.

In: European Journal of Medicinal Chemistry, Vol. 125, 05.01.2017, p. 1268-1278.

Research output: Contribution to journalArticle

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. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 125. pp. 1268-1278.
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