Artemisone—A Highly Active Antimalarial Drug of the Artemisinin Class

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

“…These are amongst the most potent anti-malarial agents known. The mechanism of action of artemisinins remains controversial [2,3] but they retain activity against parasites that have become resistant to anti-malarials such as such as chloroquine and pyrimethamine [4]. Furthermore, artemisinins can be faster acting than other drugs malarial treatments [5,6].…”

“…It is significantly more active against Plasmodium falciparum than other derivatives [4,8,9], has almost negligible toxicity [10], and is prepared in a three step process from the parent ART.…”

A Partial Convergence in Action of Methylene Blue and Artemisinins: Antagonism with Chloroquine, a Reversal with Verapamil, and an Insight into the Antimalarial Activity of Chloroquine

“…[1] These artemisinins and the newer clinically tested derivative artemisone 5 [2] are transformed by catalytic methylene blue (MB)-excess ascorbate (AA) 14 or N-benzyl-1,4-dihydronicotinamide (BNAH) 15 in aqueous buffer (pH 7.4) into singleelectron-transfer or two-electron reduction products ( Figure 1). [3] The active intermediates are leucomethylene blue (LMB) 7 and the corresponding radical for the AA reactions.…”

Evidence for a Common Non‐Heme Chelatable‐Iron‐Dependent Activation Mechanism for Semisynthetic and Synthetic Endoperoxide Antimalarial Drugs

“…However, the antagonism was more pronounced for some compounds; for example, the combination of artemisone (4) and DFO was found to be moderately (but reproducibly) antagonistic, whilst the combination of artemisone and DFP produced a significantly greater degree of antagonism (Figure 1 D). In view of the apparent resistance of artemisone to iron activation in vitro [29] and because the iron chelators themselves display antimalarial activity, we needed to rule out any possible nonspecific effects of the iron chelators (it is possible, for example, that the endoperoxides could antagonize the activity of the iron chelators). To address this issue we examined the antagonism of artemisone (and artesunate) by DFP over the much shorter time period of three hours, conditions which had zero effect on parasite viability.…”

“…To our knowledge, this is the first direct evidence in malaria parasites that support the role of non-heme iron in the intraparasitic activation process of all endoperoxides, including the artemisone-like semisynthetic compounds which appear to be resistant to degradation mediated by biomimetic ferrous sulfate. [29] Having demonstrated clear antagonism for both fluorescently tagged and untagged probe derivatives, we then set about investigating the intraparasitic sites of accumulation of representative examples as well as the role of iron chelators in modulating cellular accumulation.…”