- Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway
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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.
- Lin, Lan,Lu, Wenyu,Dai, Tianzhi,Chen, Huan,Wang, Tong,Yang, Li,Yang, Xuelian,Liu, Ying,Sun, Dequn
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- Artemisinin derivatives containing piperazine ring and fluorine element, and preparation method and application of artemisinin derivatives
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The invention provides artemisinin derivatives containing a piperazine ring and a fluorine element, and a preparation method and an application of the artemisinin derivatives. The structures of the compounds are verified through 1H NMR, 13C NMR and HRMS technologies, and in vitro cytotoxicity to MCF-7, A549, PC12, SH-SY5Y, U87MG, U118MG and HCT116 cancer cell lines is evaluated through MTT analysis. Results show that the artemisinin derivatives provided by the invention can more effectively inhibit the growth of cancer cell lines than artemisinin, and has potential application value in preparation of antitumor drugs.
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Paragraph 0079; 0111; 0114; 0115
(2020/04/06)
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- 1-Aziridine carboxylic acid derivatives with immunostimulant activity
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2-Substituted-1-aziridine-carboxylic acid esters exhibiting immuno-stimulant activity and of the formula STR1 wherein X is a carbamoyl or alkoxycarbonyl radical, and R1 is an aliphatic hydrocarbon radical optionally substituted by halogen, alkoxy, amino, carbamoyloxy, cycloalkyl, hydroxyl, an imido or heterocyclic radical, cycloalkyl; or aryl, aralkyl, aryloxyalkyl or arylthioalkyl wherein the aryl moiety is optionally substituted by halogen, alkyl, alkoxy, hydroxyl, amino, nitro, cyano, acyl, carbalkoxy, thioalkyl, alkylsulphonyl, phenyl or trifluoromethyl. Counterparts where X is --CN and R1 is as above, except for ethyl, are also new.
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