How Chinese scientists discovered qinghaosu (artemisinin) and developed its derivatives? What are the future perspectives?
ABSTRACT Since the middle of this century and especially since the 1960s and 1970s. Chinese scientists have put considerable effort and resources into the search for new antimalarial compounds extracted from Chinese traditional herbs. Archaeological findings indicate that qinghao (Artemisia annua L.) has been used as a traditional remedy in China for over two thousand years. Its antimalarial principle was finally isolated in 1971 and named artemisinin or qinghaosu (meaning the principle of qinghao in Chinese). Its rapid action, low toxicity and powerful effect against falciparum malaria made it a favored subject for research. In 1976, the unique structure of the molecule, characterized by an endoperoxide and an alternative O-C-O-C segment, was identified. The specific lactone reduction discovered during the determination of the structure opened the way for the synthesis of qinghaosu derivatives, and thereafter a series of more active and more oil- or water-soluble derivatives was developed. Subsequent studies of the structure/activity relationship led to the discovery of dihydroartemisinin, artemether and artesunate. Now qinghaosu and these three derivatives are being used around the world as effective new antimalarial drugs in the fight against falciparum malaria, including multi-drug-resistant Plasmodium falciparum. At the present time new qinghaosu analogues or derivatives are being developed and studies of their structure/activity relationships, their antimalarial mechanisms, their interaction with ferrous ions and the DNA damage associated with these processes are being actively pursued. In addition, recent studies also indicate that some qinghaosu derivatives have other bioactivities, including antiparasitic (against Schistosoma japonicum, Toxoplasma gondii and so on) and anticancer activities. Research into qinghaosu and its derivatives has already produced and will no doubt continue to produce results of the utmost importance in the fight against malaria and other diseases.
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ABSTRACT: Artemisinin (ART) based combination therapy (ACT) is used as the first line treatment of uncomplicated falciparum malaria in over 100 countries and is the cornerstone of malaria control and elimination programs in these areas. However, despite the high potency and rapid parasite killing action of ART derivatives there is a high rate of recrudescence associated with ART monotherapy and recrudescence is not uncommon even when ACT is used. Compounding this problem are reports that some parasites in Cambodia, a known foci of drug resistance, have decreased in vivo sensitivity to ART. This raises serious concerns for the development of ART resistance in the field even though no major phenotypic and genotypic changes have yet been identified in these parasites. In this article we review available data on the characteristics of ART, its effects on Plasmodium falciparum parasites and present a hypothesis to explain the high rate of recrudescence associated with this potent class of drugs and the current enigma surrounding ART resistance.12/2012; 2:249-255. DOI:10.1016/j.ijpddr.2012.01.001
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ABSTRACT: Artesunate is one of the main antimalarial drugs used in several countries. It is a semisynthetic compound derived from artemisinin, a substance extracted from the Chinese plant, Artemisia annua L. Despite the widespread use of artesunate as an antimalarial drug, there is a lack of data regarding its genotoxic effects in human lymphocytes. Therefore, in this study, we used the comet assay and micronucleus test to evaluate the possible genotoxic effects of artesunate in cultured human lymphocytes. In addition, cell death by necrosis and apoptosis was also assessed. Cells exposed to different concentrations of artesunate showed a significant concentration-dependent increase (P < 0.05) in DNA damage index and micronuclei frequency. A significant increase in the frequency of apoptotic and necrotic cells was also observed. Our results showed that artesunate is a genotoxic and cytotoxic compound in cultured human lymphocytes.Environmental and Molecular Mutagenesis 08/2011; 52(7):590-4. DOI:10.1002/em.20659 · 2.55 Impact Factor
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ABSTRACT: Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.Evidence-based Complementary and Alternative Medicine 03/2011; 2011:403709. DOI:10.1093/ecam/neq056 · 2.18 Impact Factor