Qinghaosu derivatives antimalarial activity

Some C-11 substituted qinghaosu and its derivatives were prepared and tested against P. berghei in Their lower antimalarial activity may be attributed... 

Antimalarial Activity and the Free Radical Reaction of Qinghaosu and Its Derivatives... 

Posner et al. have synthesized the 3-methyl-derivatives of qinghaosu and found that the antimalarial activity of 3p-methyl derivative in vitro was about the same as qinghaosu however, the activity of the 3a-methyl- or 3,3-dimethy-derivative was at least two orders less than that of qinghaosu. This difference was supposed to come from the availability of the C-3 free radical for the later derivatives, but it was not mentioned whether these bio-inactive compounds were also inert in the reaction with ferrous ion. ... 

Artemisia annua, known in China as Qinghaosu, contains artemisinin, which has antimalarial activity. Several derivatives of the original compound have proved effective in the treatment of Plasmodium falciparum malaria and are currently available in a variety of formulations artesunate (intravenous, rectal, oral), artelinate (oral), artemisinin (intravenous, rectal, oral), dihydroartemisinin (oral), arte-mether (intravenous, oral, rectal), and artemotil (intravenous). Artemisinic acid (qinghao acid), the precursor of artemisin, is present in the plant in a concentration up to 10 times that of artemisinin. Several semisynthetic derivatives have been developed from dihydroartemisinin (11). The artemisinin derivatives are the subject of a separate monograph. 

Qinghaosu is a sesquiterpene 1,2,4-trioxane simulating the peroxide linkage, which is an important structural requirement for antimalarial activity. Further, qinghaosu and its synthetic derivatives suffer from various limitations such as high rate of recrudescence, poor oral absorption, short half-life and embiyo-toxicity [65]. These facts led to an intense search for better antimalarials derived from simple 1,2,4-triox-anes (38). This class of compounds have been extensively studied by Jefford et al. [66-69] and others [70-75] some of them show marked in vitro and in vivo antimalarial activities [62,65]. 

Artemisinin (qinghaosu) provides a more recent example of a plant-derived antimalarial agent. Based on the reputed antimalarial use of Artemisia annua in the Chinese system of traditional medicine, artemisinin was isolated from the plant as the active compound, developed as a drug, and released for clinical use as a blood schizonticide (66-68). Artemisinin is a... 

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