A golden phoenix arising from the herbal nest — A review and reflection on the study of antimalarial drug Qinghaosu

Liu, Ying; Wu, Yunying

doi:10.1007/s11458-010-0214-5

Cited by 17 publications

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“…After screening of over 5000 traditional Chinese medicines, Qinghaosu (QHS), an antimalarial principle, was isolated from Artemisia annua L in 1972 [1,2] . At the end of 1975, its unique chemical structure was elucidated, as a sesquiterpene lactone bearing a peroxy group, quite different from that of all known antimalarial drugs [3] .…”

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“…QHS suppository in 1986; artemether oil injection and sodium artesunate aqueous injection in 1987 were approved as new antimalarial drugs. Since then, other new antimalarial drugs such as dihydroartemisinin, coartem (artemether and benflumetol), co-naphthoquine (naphthoquine phosphate and QHS), compound-dihydroartemisinin were successively developed in China [1,2] .…”

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“…So far, the successful examples are artemether and artesunate, which were found to be effective in the treatment of Schistosomiasis [34,35] . From 1993, artemether and artesunate were studied in randomized, double-blind, placebo-controlled trials in China, and approved as the prophylactic drugs for schistosomiasis japonica in 1996 [2] . Afterwards, they were found to have similar activity against S mansoni and S haematobium in other countries [36] .…”

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Qinghaosu (artemisinin): Chemistry and pharmacology

2012

Acta Pharmacol Sin

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Qinghaosu and its derivatives are widely used in the world as a new generation of antimalarial drug. Up to now, some important progresses of Qinghaosu research have been made, including synthesis of new Qinghaosu derivatives and analogs, investigation on their bioactivities and mode of actions. The present review briefly describes these efforts made by researchers in China, particularly in this Institute.Keywords: Qinghaosu; artemisinin; structure modification; antimalarial activity; anticancer activity; immunosuppressive activity; mode of action Acta Pharmacologica Sinica (2012) 33: 1141-1146; doi: 10.1038/aps.2012.104; published online 27 Aug 2012On 23rd May 1967, China established National Steering Group on antimalarial drug research, more than 60 institutes and 500 researchers joined in this project. After screening of over 5000 traditional Chinese medicines, Qinghaosu (QHS), an antimalarial principle, was isolated from Artemisia annua L in 1972 [1,2] . At the end of 1975, its unique chemical structure was elucidated, as a sesquiterpene lactone bearing a peroxy group, quite different from that of all known antimalarial drugs [3] .Early pharmacological and clinic studies showed QHS have rapid onset of action, low toxicity and high effect on both drug-resistant and drug-sensitive malaria. However, its shortcomings (poor solubility in water or oil; high rate of parasite recrudescence) needed to be overcome. In 1976, our Institute was charged with this important mission, and a research in relationship between chemical structure and activity immediately started.First of all, the function of peroxy group for antimalarial activity was examined. The negative result of deoxyqinghaosu (Scheme 1) against P berghei in mice demonstrated that the peroxy group was essential. Soon afterwards, it was found that some other simple peroxides including monoterpene ascaridol had no antimalarial activity. These experimental results proved peroxy group to be an essential but not a sufficient factor. At that time, we noted the molecule contained a rare segment -O-C-O-C-O-C=O, and realized that whole molecular skeleton might play an important role for antimalarial activity.When dihydroartemisinin (DHA) was found to be more active than QHS, but was still with poor solubility and lower stability (as a lactol) than QHS, we decided to prepare its derivatives. In 1976-1977, over 50 derivatives of DHA were synthesized (Scheme 1) and evaluated [4,5] .The first 25 compounds (in oil solution) were tested in mice infected chloroquine-resistant P berghei though intramuscular injection [6] . Most of these derivatives showed higher activity than QHS (SD 50 6.20 mg/kg) and DHA (SD 50 3.65 mg/kg). In the ether series, SM 224 (R=CH 3 , SD 50 1.02 mg/kg) is more

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Qinghaosu (artemisinin): Chemistry and pharmacology

2012

Acta Pharmacol Sin

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“…Qinghaosu (QHS, artemisinin, 1 ) is a sesquiterpene endoperoxide discovered by Chinese scientists in the early 1970s (Figure ) . Its structure is completely different from that of traditional antimalarials and shows high potency in the treatment of even multidrug resistant cases.…”

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A Hydrogen Peroxide Based Access to Qinghaosu (Artemisinin)

Hao

Han

et al. 2011

Org. Lett.

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Attachment of H(2)O(2) onto the highly hindered quaternary C-12a in an advanced qinghaosu (artemisinin) precursor has been achieved through a facile perhydrolysis of a spiro epoxy ring with the aid of a previously unknown molybdenum species without involving any special equipment or complicated operations. The resultant β-hydroxyhydroperoxide can be further elaborated into qinghaosu, illustrating an entry fundamentally different from the existing ones to this outstanding natural product of great importance in malaria chemotherapy.

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“…Many natural products have been found to possess antineoplastic activity with minimal side effects [3]. Artemisinin, a well-known anti-malarial agent, has been reported to possess a potent and broad antitumor spectrum against human cancer cell lines [4]. However, the drawback, such as drug resistance or unsatisfactory metabolism, constrains artemisinin to be employed as an antitumor drug clinically.…”

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Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry

Tian

Liang

et al. 2016

Molecules

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Abstract:In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC 50 values in the 0.05-125.40 µM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one-to 10-fold greater activity than under normoxic condition. Compounds 10a-e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.

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A golden phoenix arising from the herbal nest — A review and reflection on the study of antimalarial drug Qinghaosu

Cited by 17 publications

References 386 publications

Qinghaosu (artemisinin): Chemistry and pharmacology

Qinghaosu (artemisinin): Chemistry and pharmacology

A Hydrogen Peroxide Based Access to Qinghaosu (Artemisinin)

Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry

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