Abstract:
:Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC50 = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC50 = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca2+ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Lin L,Lu W,Dai T,Chen H,Wang T,Yang L,Yang X,Liu Y,Sun Ddoi
10.1016/j.bioorg.2020.104496subject
Has Abstractpub_date
2021-01-01 00:00:00pages
104496eissn
0045-2068issn
1090-2120pii
S0045-2068(20)31794-6journal_volume
106pub_type
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