Novel Chalcone-Phenazine Hybrids Induced Ferroptosis in U87-MG Cells through Activating Ferritinophagy |
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Authors: | Chunhua Zhang Qifan Ding Zhuolu Xia Hengyu Wang Feng Jiang Yuanyuan Lu |
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Affiliation: | 1. School of Engineering, China Pharmaceutical University, Nanjing, 210009 China;2. School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009 China |
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Abstract: | Thirty-seven novel chalcone-phenazine hybrid molecules ( C1∼C13 and F1∼F24 ) with 1,2,3-triazole or ethyl group as linkers were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against U87-MG cancer cell lines in vitro, in which compound C4 were found to have the best antiproliferative activity. SAR study indicated 1,2,3-triazole group may be crucial for enhancing compounds’ cytotoxicity. C4 was verified to induce ferroptosis in U87-MG cells by transcription, lipid peroxidation, lipid ROS assays. Furthermore, C4 was up-regulated LC3-II, degradated FTH1, and then increasing iron resulted in the down-regulation of NCOA4. Together, all above evidences highlighted the potential of compound C4 that triggered ferroptosis by activating ferritinophagy against U87-MG cells. |
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Keywords: | phenazine chalcone U87-MG ferroptosis ferritinophagy |
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