Synthesis, antimalarial activity and cytotoxicity of 10-aminoethylether derivatives of artemisinin

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• 作者：Theunis T. Cloete ; J. Wilma Breytenbach ; Carmen de Kock ; Peter J. Smith ; Jaco C. Breytenbach ; David D. N¡¯Da
• 关键词：Artemisinin ; Plasmodium falciparum ; Microwave ; Malaria
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：1 August, 2012
• 年：2012
• 卷：20
• 期：15
• 页码：4701-4709
• 全文大小：461 K

文摘

In this study, a series of 11 10-aminoethylether derivatives of artemisinin were synthesised and their antimalarial activity against both the chloroquine sensitive (D10) and resistant (Dd2) strains of Plasmodium falciparum was determined. The compounds were prepared by introducing aliphatic, alicyclic and aromatic amine groups with linkers of various chain lengths through an ethyl ether bridge at C-10 of artemisinin using conventional and microwave assisted syntheses, and their structures were confirmed by NMR and HRMS. All derivatives proved to be active against both strains of the parasite. The highest overall activity was displayed by the short chain aromatic derivative 8 (IC₅₀ = 1.44 nM), containing only one nitrogen atom, while long chain polyamine derivatives were found to have the lowest activity against both strains. An interesting correlation between the IC₅₀, pK_a values and resistance index (RI) was found.