2. Academic Validation
  3. Design, synthesis, and biological evaluation of 1-styrenyl isoquinoline derivatives for anti-hepatocellular carcinoma activity and effect on mitochondria

Design, synthesis, and biological evaluation of 1-styrenyl isoquinoline derivatives for anti-hepatocellular carcinoma activity and effect on mitochondria

  • Eur J Med Chem. 2023 Aug 5;256:115420. doi: 10.1016/j.ejmech.2023.115420.
Yuqing Wang 1,  Lin Long 2,  Linsheng Zhuo 3,  Honghua Zhang 1,  Tian Luo 1,  Jiedan Deng 1,  Yuying Wang 4,  Zhao Li 1,  Zhen Wang 5,  Xue Peng 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou, Gansu, 730000, China.
  • 2 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • 3 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • 4 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China.
  • 5 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address: [email protected].
  • 6 School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address: [email protected].
PMID: 37182331 DOI: 10.1016/j.ejmech.2023.115420
Abstract

In this study, 18 derivatives of 1-styrene-isoquinoline were designed and synthesized from resveratrol and isoquinoline. The IC50 of compound 1c against Huh7 and SK-Hep-1 cells were 2.52 μM and 4.20 μM, respectively. Mice were treated with 650 mg/kg compound 1c, and the survival status of mice was good. Further studies showed that compound 1c could inhibit cell proliferation by arresting the cell cycle in the G2/M phase, induce cell Apoptosis, and inhibit cell migration and invasion by regulating epithelial-mesenchymal transition (EMT). It is worth noting that numbers of studies have pointed that resveratrol can trigger mitochondrial Apoptosis to induce Apoptosis of Cancer cells. Therefore, we investigated the mechanism of compound 1c induced Apoptosis of Huh7 and SK-Hep-1 cells. The results indicated that compound 1c could regulate the expression of proteins which are related to mitochondrial Apoptosis pathway and inhibit the phosphorylation of PI3K/Akt/mTOR signaling pathway. In addition, compound 1c could inhibit the growth of Huh7-xenografts, and perform a tumor inhibitory rate of 41.44% when administered 30 mg/kg once a day. This work provides a potential anti-hepatocellular carcinoma compound that warrants further investigation.

Keywords

1-Styryl isoquinoline; Apoptosis; Hepatocellular carcinoma; Mitochondria; Resveratrol.

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