2. Academic Validation
  3. Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A

Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A

  • Eur J Med Chem. 2022 Feb 5;229:114048. doi: 10.1016/j.ejmech.2021.114048.
Chen Zhou 1,  Jun-Yuan Zhang 1,  Han-Bo Liu 1,  Xiang-Yu Tian 2,  Yue Liu 1,  Ya-Lei Wang 1,  Zi-Jun Zheng 1,  Ni Wang 1,  Zhi-Jia Wang 1,  Xia Xu 3,  Hong-Min Liu 4,  Yu Ke 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Henan Key Laboratory of Drug Quality Control & Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Ministry of Education of China, Zhengzhou, 450001, China.
  • 2 The First Affiliated Hospital of Zhengzhou University, Henan Province, Zhengzhou, 450052, China.
  • 3 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Henan Key Laboratory of Drug Quality Control & Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Ministry of Education of China, Zhengzhou, 450001, China. Electronic address: xuxia@zzu.edu.cn.
  • 4 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Henan Key Laboratory of Drug Quality Control & Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Ministry of Education of China, Zhengzhou, 450001, China. Electronic address: liuhm@zzu.edu.cn.
  • 5 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Henan Key Laboratory of Drug Quality Control & Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Ministry of Education of China, Zhengzhou, 450001, China. Electronic address: ky@zzu.edu.cn.
PMID: 34954589 DOI: 10.1016/j.ejmech.2021.114048
Abstract

Jiyuan Oridonin A (JOA) is a naturally occurring ent-kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its Anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected Cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA, the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC50 value of 0.39 ± 0.09 μM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12-induced Apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA, which would contribute to its further development as an antitumor agent.

Keywords

Anti-tumor mechanism; Fluorescent probe; Jiyuan oridonin A; Naphthalimide.

Figures
Products
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