Qinghaosu derivatives activities

When dihydroartemisinin was found to be more active than qinghaosu and the introduction of the hydroxy group into the molecular nucleus could not improve its solubility in water, three types of dihydroartemisinin derivatives were synthesized and evaluated in China (Scheme... 

The first 25 compounds (in oil solution) were tested in the mice-infected chloroquine-resistant P. berghei by administration of intramuscular injection. Most of these derivatives showed more activity than qinghaosu and dihydroartemisinin. 

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

Qinghaosu acts parasite at its intra-erythrocytic asexual stage. At this stage, the parasite takes hemoglobin as its nutritional resource, digests hemoglobin, and leaves free heme, which is then polymerized to parasite safety poly-heme (hemo-zoin). Two other points should be mentioned Over 95% iron in the human body exists as heme in the red blood cell, and the peroxide segment of 1 and its derivatives is essentially responsible for its activity. 

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. ... 

The C-centered free radical is the active species, but what target will be attacked by these radicals derived from qinghaosu and its derivatives in the biosystem is still a puzzle. This topic is an interesting one in the qinghaosu research area. 

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... 

Compounds with rearranged cadinane skeletons include the fungal antibiotic heptelidic acid (203), the most unusual endo-peroxide qinghaosu (204), which is an active principle from the Chinese medicinal herb Artemisia annua L., and koidzumiol (205). The biogenesis of the latter compound is considered to be as shown in Scheme 24. Some further derivatives of abrotanifolone (206) have also been isolated. ... 

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