East meets West: how China almost cured malaria

Burns, William R.

doi:10.1016/j.endeavour.2008.07.001

Cited by 29 publications

(18 citation statements)

References 10 publications

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“…Febrifugine was identified over 60 years ago as the active principle of one of the oldest known antimalarial herbal remedies (16). However, poor tolerability prevented the clinical use of febrifugine as a mainstay antimalarial and previous medicinal chemistry efforts failed to identify viable alternatives (17).…”

Section: Discussionmentioning

confidence: 99%

The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs

et al. 2015

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The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials.

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Section: Discussionmentioning

confidence: 99%

The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs

et al. 2015

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“…Peruvians had long used tinctures of cinchona to treat malarial fevers, but it was in 1820 that the active ingredient, quinine, was extracted and isolated from cinchona bark by the French chemists Pierre-Joseph Pelletier and Joseph Bienaimé Caventou (7). Quinine remained the drug of choice until the 1940s; however, when the Japanese seized Dutch cinchona plantations in Java during World War II, there was a vast quinine shortage, particularly in China (7). The next effective malaria treatment, chloroquine, was synthesized in 1934 at the Bayer laboratories, but it was shelved for at least a decade due to excess toxicity in humans (8).…”

Section: Figurementioning

confidence: 99%

From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria

Neill¹

2011

J. Clin. Invest.

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“…The cinchona bark was brought back to Europe in the seventeenth century and empirically used to treat fever and pain until 1820, when the French chemists Pelletier and Caventou isolated the active ingredient, quinine. For centuries to come, quinine has been used to treat malaria successfully, especially after the introduction of its synthetic derivatives at the end of the Second World War (Burns, 2008). One of these derivatives, chloroquine, was dominantly marketed by the company Rhône-Poulenc under the name of Nivaquine®, through two of its affiliates: Specia in the Francophone world and May & Baker in the Anglophone one.…”

mentioning

confidence: 99%

“…In 1967, China was at the beginning of the Cultural Revolution, but the scientists chosen to work on the 523 project were promised protection from the Red Guards; nevertheless, considering the speed at which the leaders were replaced then, these scientists (among them, Zhou Keding, the project coordinator in the Academy of Military Medical Sciences, Li Ying from the Shanghai Institute of Materia medica ...) remained cautious in keeping their work as secret as possible and avoided all communication, which could be intercepted by uncontrollable Red Guards ( History of Qinghaosu and Prof. Zhou Keding , 2008; Li & Wu, 2003; Burns, 2008). Though later, they liked joking about how they had to work in very special and unorthodox ways, they were taking considerable risks.…”

mentioning

confidence: 99%