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

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

  • Eur J Med Chem. 2017 Jan 5:125:1268-1278. doi: 10.1016/j.ejmech.2016.11.033.
Hsueh-Yun Lee 1,  Jiann-Fong Lee 1,  Sunil Kumar 1,  Yi-Wen Wu 2,  Wei-Chun HuangFu 3,  Mei-Jung Lai 4,  Yu-Hsuan Li 1,  Hsiang-Ling Huang 1,  Fei-Chiao Kuo 1,  Che-Jen Hsiao 5,  Chun-Chun Cheng 3,  Chia-Ron Yang 6,  Jing-Ping Liou 7
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 2 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 3 The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 4 Center for Translational Medicine, Taipei Medical University, Taiwan.
  • 5 Department of Pharmacology, College of Medicine, Taipei Medical University, Taiwan.
  • 6 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: cryang@ntu.edu.tw.
  • 7 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: jpl@tmu.edu.tw.
PMID: 27886544 DOI: 10.1016/j.ejmech.2016.11.033
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.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z