Design and Mechanism Study of 6c, a Novel Artesunate Derivatives, for Anti-Hepatocellular Carcinoma DOI Creative Commons

S Xiong

Journal of Hepatocellular Carcinoma, Journal Year: 2025, Volume and Issue: Volume 12, P. 149 - 167

Published: Jan. 1, 2025

Artesunate can inhibit the proliferation of various tumor cells and has practical value in developing anti-tumor drugs. However, its biological activity against hepatocellular carcinoma is weak. The efficacy effect needs to be improved. 11 compounds three types were designed synthesized. Their antitumor was detected by MTT assay vitro subcutaneous xenograft model vivo. Then, DCFH-DA probe detection NAC intervention experiments used detect ROS levels. ferroptosis inhibitor (Liproxstatin-1) study compound 6c inducing ferroptosis. Western blot observe expression apoptosis-related proteins. ability induce apoptosis Annexin V-FITC/PI double staining Hoechst 33342 experiment. on cycle arrest flow cytometry. Molecular simulations several hybrids with vascular endothelial growth factor receptor 2 (VEGFR-2) Transferrin protein 1 (TFR1) performed using MOE molecular docking software. A series new artemisinin-4-(4-substituted phenoxy) pyridine derivatives synthesized their anticancer activities tested lines (HCC) cells. Among hybrid hits activity, a representative increased reactive oxygen species (ROS) level activated mitochondrial ferroptosis, leading cell at G2/M phase. shows binding oncogenic that are overexpressed malignant epithelial tumors. Taken together, our identification promising may hold developmental potential for therapy carcinoma.

Language: Английский

Design and Mechanism Study of 6c, a Novel Artesunate Derivatives, for Anti-Hepatocellular Carcinoma DOI Creative Commons

S Xiong

Journal of Hepatocellular Carcinoma, Journal Year: 2025, Volume and Issue: Volume 12, P. 149 - 167

Published: Jan. 1, 2025

Artesunate can inhibit the proliferation of various tumor cells and has practical value in developing anti-tumor drugs. However, its biological activity against hepatocellular carcinoma is weak. The efficacy effect needs to be improved. 11 compounds three types were designed synthesized. Their antitumor was detected by MTT assay vitro subcutaneous xenograft model vivo. Then, DCFH-DA probe detection NAC intervention experiments used detect ROS levels. ferroptosis inhibitor (Liproxstatin-1) study compound 6c inducing ferroptosis. Western blot observe expression apoptosis-related proteins. ability induce apoptosis Annexin V-FITC/PI double staining Hoechst 33342 experiment. on cycle arrest flow cytometry. Molecular simulations several hybrids with vascular endothelial growth factor receptor 2 (VEGFR-2) Transferrin protein 1 (TFR1) performed using MOE molecular docking software. A series new artemisinin-4-(4-substituted phenoxy) pyridine derivatives synthesized their anticancer activities tested lines (HCC) cells. Among hybrid hits activity, a representative increased reactive oxygen species (ROS) level activated mitochondrial ferroptosis, leading cell at G2/M phase. shows binding oncogenic that are overexpressed malignant epithelial tumors. Taken together, our identification promising may hold developmental potential for therapy carcinoma.

Language: Английский

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