2. Academic Validation
  3. Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives

Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives

  • Bioorg Med Chem Lett. 2020 Feb 15;30(4):126913. doi: 10.1016/j.bmcl.2019.126913.
Xueyan Huang 1,  Keguang Cheng 2,  Lilin Liu 1,  Xu Hu 1,  Xiang Gao 1,  Haonan Li 1,  Fanxing Xu 3,  Zhanlin Li 1,  Huiming Hua 4,  Dahong Li 5
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
  • 2 State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Raod, Guilin 541004, PR China.
  • 3 Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: fanxing0011@163.com.
  • 4 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: huimhua@163.com.
  • 5 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: lidahong0203@163.com.
PMID: 31883693 DOI: 10.1016/j.bmcl.2019.126913
Abstract

To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast Cancer cells MCF-7, colon Cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 μM against the above four cells, respectively. Nevertheless, it showed an IC50 value >40 μM against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and Cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells Apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, Survivin, claspin and clusterin.

Keywords

Antiproliferative; Apoptosis; Chelidonine; Nitric oxide.

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