2. Academic Validation
  3. Design, synthesis and bioactivity evaluations of 8-substituted-quinoline-2-carboxamide derivatives as novel histone deacetylase (HDAC) inhibitors

Design, synthesis and bioactivity evaluations of 8-substituted-quinoline-2-carboxamide derivatives as novel histone deacetylase (HDAC) inhibitors

  • Bioorg Med Chem. 2023 May 1:85:117242. doi: 10.1016/j.bmc.2023.117242.
Yunpeng Zhao 1,  Zefu Yao 1,  Wandi Ren 2,  Xinying Yang 2,  Xuben Hou 1,  Shengda Cao 3,  Hao Fang 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China.
  • 2 Department of Pharmaceutical Analysis and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China.
  • 3 Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012 Jinan, Shandong, PR China; Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China. Electronic address: entcsd@sdu.edu.cn.
  • 4 Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012 Jinan, Shandong, PR China; Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China. Electronic address: haofangcn@sdu.edu.cn.
PMID: 37079967 DOI: 10.1016/j.bmc.2023.117242
Abstract

The inhibition of histone deacetylases (HDACs) has been considered a promising therapeutic strategy for treatment of many diseases, especially Cancer. In the current study, a series of 8-substituted quinoline-2-carboxamide derivatives were designed and synthesized as potent HDAC inhibitors. The most potent compound 21 g (IC50 = 0.050 µM) exhibited 3-fold greater HDAC inhibitory activity compared to the known HDAC Inhibitor Vorinostat (IC50 = 0.137 µM). Additionally, compound 21g exhibited low toxicity against normal cells(IC50 in HUVEC cell > 50 µM) and showed good liver microsomal stability, therefore, may serve as a new lead compound for further development.

Keywords

Anti-cancer; HDAC inhibitor; Quinoline derivativve.

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