2. Academic Validation
  3. Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer

Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer

  • Eur J Med Chem. 2022 Jan 15:228:113960. doi: 10.1016/j.ejmech.2021.113960.
Ziyi Liang 1,  Fang Lei 2,  Jiedan Deng 2,  Honghua Zhang 2,  Yuqing Wang 2,  Junfang Li 2,  Tao Shi 2,  Xiaoyan Yang 3,  Zhen Wang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
  • 2 School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
  • 3 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address: yyangxiaoyan@163.com.
  • 4 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address: zhenw@lzu.edu.cn.
PMID: 34774339 DOI: 10.1016/j.ejmech.2021.113960
Abstract

Gastric Cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric Cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of Topoisomerase 1 (Top1), effectively induced Apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric Cancer.

Keywords

Evodiamine derivatives; Gastric cancer; Top1 inhibitor.

Figures