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• W2068064554 abstract "Elucidation of the principal targets of the action of the antimalarial drug artemisinin is an ongoing pursuit that is important for understanding the action of this drug and for the development of more potent analogues. We have examined the chemical reaction of Hb with artemisinin. The protein-bound haem in Hb has been found to react with artemisinin much faster than is the case with free haem. It appears that the uptake of Hb and the accumulation of artemisinin into the food vacuole, together with the preferred reactivity of artemisinin with haem in Hb, may make Hb the primary target of artemisinin's antimalarial action. Both monoalkylated (HA) and dialkylated (HAA) haem derivatives of artemisinin have been isolated. These ‘haemarts’ bind to PfHRP II (Plasmodium falciparum histidine-rich protein II), inhibiting haemozoin formation, and possess a significantly decreased ability to oxidize ascorbic acid. The accelerated formation of HAA from Hb is expected to decrease the ratio of haem to its alkylated derivatives. The haemarts that are generated from ‘haemartoglobins’ may bring about the death of malaria parasite by a two-pronged effect of stalling the formation of haemozoin by the competitive inhibition of haem binding to its templates and creating a more reducing environment that is not conducive to the formation of haemozoin." @default.
• W2068064554 created "2016-06-24" @default.
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• W2068064554 date "2005-01-07" @default.
• W2068064554 modified "2023-09-30" @default.
• W2068064554 title "Reaction of artemisinin with haemoglobin: implications for antimalarial activity" @default.
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• W2068064554 doi "https://doi.org/10.1042/bj20041170" @default.
• W2068064554 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1134711" @default.
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