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G6PD Gene - GeneCards | G6PD Protein | G6PD Antibody

[101] The relatively high doses of fosmidomycin required for parasite clearance compared with chloroquine and the unfavorable pharmacokinetic properties prompted researchers to modify this lead.

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During World War I, Java and its valuable quinine stores fell into Japanese forces. As a result, the German troops in East Africa suffered heavy casualties from malaria. In a bid to have their own antimalarial drugs, the German government initiated research into quinine substitutes and entrusted it to Bayer Dye Works. Most of the work was done at Bayer Farbenindustrie A.G. laboratories in Eberfeld, Germany. Several thousands of compounds were tested and some were found to be useful. Plasmochin naphthoate (Pamaquine) in 1926 and quinacrine, mepacrine (Atabrine) in 1932 were the first to be found. Plasmochin, an 8 amino quinoline, was quickly abandoned due to toxicity, although its close structural analog primaquine is now used to treat latent liver parasites of P. vivax and P. ovale. Atabrine, although found superior and persisting in the blood for at least a week, had to be abandoned due to side effects like yellowing of the skin and psychotic reactions. The breakthrough came in 1934 with the synthesis of Resochin (chloroquine) by Hans Andersag, followed by Sontochin or Sontoquine (3 methyl chloroquine). These compounds belonged to a new class of antimalarials known as 4 amino quinolines. But Farben scientists overestimated the compounds’ toxicity and failed to explore them further. Moreover, they passed the formula for Resochin to Winthrop Stearns, Farben’s U.S. sister company, in the late 1930s. Resochin was then forgotten until the outbreak of World War II.

Antimicrobial Agents III - Wikiversity

Chloroquine - Wikipedia

An appeal for help from Ho Chi Minh to Zhou En Lai during the Vietnam War triggered the work on this herb and in 1967, the Chinese scientists set up Project 523. The active ingredient of was isolated by Chinese scientists in 1971. An ethyl ether extract of fed to mice infected with the rodent malaria strain, Plasmodium berghei, was found to be as effective as chloroquine and quinine at clearing the parasite. The human trails were published in the Chinese Medical Journal in 1979. Many active derivatives of artemisinin have since been synthesized and it is today a very potent and effective antimalarial drug, particularly against drug resistant malaria in many areas of southeast Asia. So far, clinically relevant genetic resistance to artemisinin has not been reported, although tolerance has been noted.

Diethyl malonate is used in organic synthesis for the preparation of alpha-aryl malonates, mono-substituted and di-substituted acetic acid, barbiturates and artificial flavorings. It is also involved in the synthesis of pharmaceuticals like chloroquine, butazolidin and barbital. It acts as intermediate in the synthesis of vitamin B1, vitamin B6, non-steroidal anti-inflammatory agents agrochemicals and perfumes. In Knoevenagel condensation reaction, it reacts with benzaldehyde to get diethyl benzylidenemalonate.

all_antimalarial_drugs [TUSOM | Pharmwiki]

Resistance to chloroquine is now very common against strains of P

The success of chloroquine led to the exploration of many (nearly 15000) compounds in the United States and another 4-aminoquinoline Camoquin (amodiaquin) was discovered. Studies on 8-aminoquinolines led to the discovery of Primaquine by Elderfield in 1950. Meanwhile, British investigators at ICI also carried out extensive studies on malaria drugs and Curd, Davey and Rose synthesised antifolate drugs proguanil or Paludrine (chlorguanide hydrochloride) in 1944 and Daraprim or Malocide (pyrimethamine) was developed in 1952. However, resistance to proguanil was observed within a year of introduction in Malaya in 1947. P. falciparum strains resistant to pyrimethamine, and cross-resistant to proguanil emerged in 1953 in Muheza, Tanzania. Sulfadoxine-pyrimethamine combination was introduced in Thailand in 1967. Resistance to this was first reported in Thailand later that year and spread quickly throughout Southeast Asia and recently appeared in Africa.

With the German invasion of Holland and the Japanese occupation of Java, the Allied forces were cut off from quinine. This stimulated a renewed search for other antimalarials both in the United Kingdom and in the United States. After the Allied occupation of North Africa, the French soldiers raided a supply of German manufactured Sontochin in Tunis and handed it over to the Americans. Winthrop researchers made slight adjustments to the captured drug and this new formulation was called chloroquine. Later, it was found to be identical to the older and supposedly toxic Resochin. However it was not available for the troops until the end of the War. But following World War II, chloroquine and DDT became the two principal weapons in the global malaria control campaign.

falciparum, and uncommon but increasing for P vivax
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