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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 (IC(50)=1.44nM), 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 IC(50), pK(a) values and resistance index (RI) was found., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The in vitro antimalarial activity of a series of 2- and 8-trifluoromethyl- and 2,8-bis(trifluoromethyl)quinoline-4-(5-pyrimidino) and N4-ethyl-5-nitroimidazolo)methylene ketones was assessed against the chloroquine-sensitive strain (D10) of Plasmodium falciparum. Although the in vitro antimalarial activity of these compounds is more or less of the same order of magnitude, derivatives containing two trifluoromethyl groups achieve a slightly higher in vitro activity than compounds with one trifluoromethyl group, with 2,8-bis(trifluoromethyl) quinoline-4-(N4-ethyl-5-nitroimidazolo) methylene and 2,8-bis(trifluoromethyl) quinoline-4-(5-pyrimidino) ketones showing IC50 of 4.8 and 5.2 micrograms/ml, respectively. These compounds seem to bind to DNA by intercalation.

Abstract: Series of bisquinolines 4–15 and bispyrrolo[1,2a]quinoxalines 16–20 containing various polyamine linkers were synthesized. The aqueous solubility and distribution coefficient were experimentally determined. The compounds were screened for antimalarial activity alongside chloroquine against D10 and Dd2 strains of Plasmodium falciparum. The growth inhibitory effects of biscompounds 4–9 were assessed against various cancer cell lines. The aqueous solubility was found to increase with an increase in potential proton.ation sites. Bisquinolines 8 and 9 featuring triethylenetetramine and N,N′-bis(3-aminopropyl)ethylene-diamine linkers, respectively, were the most active of all synthesized compounds. They were found as potent as chloroquine against D10 but significantly more potent against the Dd2 strain, with good selectivity towards parasitic cells. Compound 4 containing a diethylenetriamine bridge displayed the most important anticancer activity of the series, and was a more effective antiproliferative inhibitor than etoposide against all three TK10, UACC62 and MCF7 cancer cell lines. [Copyright &y& Elsevier]