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

doi:10.1016/j.ejmech.2016.11.033

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 journal › Article › peer-review

38 Scopus citations

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 language	English (US)
Pages (from-to)	1268-1278
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	125
DOIs	https://doi.org/10.1016/j.ejmech.2016.11.033
State	Published - 2017
Externally published	Yes

Keywords

3-Aroylindoles
Anticancer agents
Histone deacetylase inhibitors
Tubulin polymerization inhibition

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.ejmech.2016.11.033

Cite this

Lee, H. Y., Lee, J. F., Kumar, S., Wu, Y. W., HuangFu, W. C., Lai, M. J., Li, Y. H., Huang, H. L., Kuo, F. C., Hsiao, C. J., Cheng, C. C., Yang, C. R., & Liou, J. P. (2017). 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity. European Journal of Medicinal Chemistry, 125, 1268-1278. https://doi.org/10.1016/j.ejmech.2016.11.033

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

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.",

keywords = "3-Aroylindoles, Anticancer agents, Histone deacetylase inhibitors, Tubulin polymerization inhibition",

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

note = "Funding Information: This research were supported by the National Science Council of the Republic of China (grant no. MOST 103-2113-M-038 -001 -MY3 ). Publisher Copyright: {\textcopyright} 2016 Elsevier Masson SAS",

year = "2017",

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AU - Lee, Hsueh Yun

AU - Lee, Jiann Fong

AU - Kumar, Sunil

AU - Wu, Yi Wen

AU - HuangFu, Wei Chun

AU - Lai, Mei Jung

AU - Li, Yu Hsuan

AU - Huang, Hsiang Ling

AU - Kuo, Fei Chiao

AU - Hsiao, Che Jen

AU - Cheng, Chun Chun

AU - Yang, Chia Ron

AU - Liou, Jing Ping

N1 - Funding Information: This research were supported by the National Science Council of the Republic of China (grant no. MOST 103-2113-M-038 -001 -MY3 ). Publisher Copyright: © 2016 Elsevier Masson SAS

PY - 2017

Y1 - 2017

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