2. Academic Validation
  3. Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents

Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents

  • J Med Chem. 2022 Jun 9;65(11):7975-7992. doi: 10.1021/acs.jmedchem.2c00520.
Fang Lei 1,  Yongxia Xiong 2,  Yuqing Wang 1,  Honghua Zhang 1,  Ziyi Liang 3,  Junfang Li 1,  Yiyue Feng 1,  Xiangyong Hao 4,  Zhen Wang 1 2 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 3 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • 4 Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China.
PMID: 35639640 DOI: 10.1021/acs.jmedchem.2c00520
Abstract

Evodiamine has many biological activities. Herein, we synthesize 23 disubstituted derivatives of N14-phenyl or the E-ring of evodiamine and conduct systematic structure-activity relationship studies. In vitro antiproliferative activity indicated that compounds F-3 and F-4 dramatically inhibited the proliferation of Huh7 (IC50 = 0.05 or 0.04 μM, respectively) and SK-Hep-1 (IC50 = 0.07 or 0.06 μM, respectively) cells. Furthermore, compounds F-3 and F-4 could double inhibit topoisomerases I and II, inhibit invasion and migration, block the cell cycle to the G2/M stage, and induce Apoptosis as well. Additionally, compounds F-3 and F-4 could also inhibit the activation of HSC-T6 and reduce the secretion of collagen type I to slow down the progression of liver fibrosis. Most importantly, compound F-4 (TGI = 60.36%) inhibited tumor growth more significantly than the positive drug sorafenib. To sum up, compound F-4 has excellent potential as a strong candidate for the therapy of hepatocellular carcinoma.

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