3:;1493-23-8Relevant articles and documents
Artemisinin and a series of novel endoperoxide antimalarials exert early effects on digestive vacuole morphology
Crespo, Maria Del Pilar,Avery, Thomas D.,Hanssen, Eric,Fox, Emma,Robinson, Tony V.,Valente, Peter,Taylor, Dennis K.,Tilley, Leann
, p. 98 - 109 (2008)
Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum. A trans-epoxide with respect to the peroxide linkage increases the activity compared to that of its cis-epoxy counterpart or the parent endoperoxide. The novel endoperoxides do not show a strong interaction with artemisinin. We have compared the mechanism of action of the novel endoperoxides with that of artemisinin. Electron microscopy reveals that the novel endoperoxides cause the early accumulation of endocytic vesicles, while artemisinin causes the disruption of the digestive vacuole membrane. At longer incubation times artemisinin causes extensive loss of organellar structures, while the novel endoperoxides cause myelin body formation as well as the accumulation of endocytic vesicles. An early event following endoperoxide treatment is the redistribution of the pH-sensitive probe LysoSensor Blue from the digestive vacuole to punctate structures. By contrast, neither artemisinin nor the novel endoperoxides caused alterations in the morphology of the endoplasmic reticulum nor showed antagonistic antimalarial activity when they were used with thapsigargin. Analysis of rhodamine 123 uptake by P. falciparum suggests that disruption of the mitochondrial membrane potential occurs as a downstream effect rather than as an initiator of parasite killing. The data suggest that the digestive vacuole is an important initial site of endoperoxide antimalarial activity. Copyright
A Rapid Injection NMR Study of the Reaction of Organolithium Reagents with Esters, Amides, and Ketones
Plessel, Kristin N.,Jones, Amanda C.,Wherritt, Daniel J.,Maksymowicz, Rebecca M.,Poweleit, Eric T.,Reich, Hans J.
supporting information, p. 2310 - 2313 (2015/05/27)
Unexpectedly high rates of reaction between alkyllithium reagents and amides, compared to esters and ketones, were observed by Rapid Inject NMR and competition experiments. Spectroscopic investigations with 4-fluorophenyllithium (ArLi, mixture of monomer and dimer in THF) and a benzoate ester identified two reactive intermediates, a homodimer of the tetrahedral intermediate, stable below -100°C, and a mixed dimer with ArLi. Direct formation of dimers suggested that the ArLi dimer may be the reactive aggregate rather than the usually more reactive monomer. In contrast, RINMR experiments with ketones demonstrated that the ArLi monomer was the reactive species. (Chemical Equation Presented).
Relative basicities of ortho-, meta-, and para-substituted aryllithiums
Gorecka-Kobylinska, Joanna,Schlosser, Manfred
experimental part, p. 222 - 229 (2009/04/11)
(Chemical Equation Presented) The relative basicities of aryllithiums bearing methoxy, chlorine, fluorine, trifluoromethyl and trifluoromethoxy substituents at the ortho, meta, and para positions have been assessed. To this end, two aryllithiums of compar
