Anti-malarial

The sodium salt of ethyl acetoacetate in ethanol at 0°C reacts with ethylene oxide to give 2-acet5l-4-butyrolactone, an intermediate for vitamin and anti-malarials (75). 

It will be interesting to see how much of this activity will survive in post-war conditions, especially in competition with new, synthetic, anti-malarial drugs developed during the war and revival of the Java cinchona industry, which is apparently making progress. 

Similarly Magidson et al., in a series of 6-methoxyquinolines substituted at C by the chain. NH—[CHjJn—NEtj found in anti-malarial tests in siskins, the following changes in the chemotherapeutic index — ... 

The central. CHOH. group in the cinchona alkaloids seems to be essential to anti-malarial activity Conversion into quinicines [quinatoxines (I) — (VII)] destroys activity and so do such changes as. CHOH. — . CHCl. (cinchona chlorides) or. CHOH. — . CHj. (deoxy-cinchona bases) or. CHOH. — . CO. quina-ketones), or acylation of the hydroxyl group except in the case of quinine ethylcarbonate. 

The effect of change in the spatial relations at C and C is not clear since, as explained above, there is doubt as to the relative activities of the components of the two pairs, quinine and quinidine, and cinchonidine and cinchonine, but epf-C -quinine and epi-C -quinidine are only slightly active or, according to Dirscherl and Thron, inactive. This result supports Neeman s view that for anti-malarial activity the direction of rotation must be the same at C and C but that does not explain the... 

Work also prepared a series of carbinolamines and polyamines without a quinoline nucleus but, in other respects, conforming in type and range of molecular weight, with quinoline compounds known to possess plasmocidal activity. As none of these were active, it seems clear that the quinoline nucleus in the cinchona alkaloids and in certain synthetic anti-malarials is a potent factor in the production of plasmocidal action. Later the same author made (1942) a series of lepidylamine derivatives of the form R. Q. CHj. NH[CH2] . NEtj, which were found to be inactive, in spite of their similarity to the active examples of the type R. Q. NH[CH2] . NEt2 prepared by Magidson and Rubtzow. Rubtzow (1939) has also shown that an isomeride of dihydroquinine (II) with the quinuclidine nucleus attached via the carbinol group at C in the quinoline nucleus was inactive in an infection of Plasmodium prcecox in finches. 

Much work has also 4)een done bearing directly or indirectly on the mode of action of quinine and other anti-malarial drugs. The absorption, distribution and metabolism of quinine has been investigated by various workers of whom Kelsey, Ceiling, Oldham and Dearborn (1944)... 

As a practical result there are now at least six synthetic anti-malarial drugs available to malariologists, including the three pre-war drugs, pamaquln, mepacrine and plasmocide. 

Of the other cinchona bases, the dextrorotatory forms cinchonine and quinidine have been used as anti-malarial drugs in cases of idiosyncrasy to quinine, a subject to which Dawson has given much attention. Quinidine is used to eontrol auricular fibrillation, and its value for this purpose in comparison with dihydroquinidine has been investigated by several workers. Dawes has recently devised a method of testing... 

Coulthard for amoebicidal action. Each kind of activity increases to a peak as the series is ascended and then diminishes. In the 0-n-alkyl series the peak is at 0-n-butylharmol for Bacillus typhosus, at 0-n-amyl-harmol for Staphylococcus aureus and at 0-n-nonylharmol for Entamoeba histolytica. In the 0-io-diethylaminoalkyl series the peak for B. typhosus is at 0-to-diethylaminononylharmol. No trypanocidal or anti-malarial action was observed in a selection of the compounds tested. ... 

The barks of Alstoiiia species (Apocyiiaceae) had a considerable reputation throughout the tropics as effective anti-malarial drugs, which led to their inclusion in the British Pharmacopoeia, 1914, and to their chemical examination by various workers. The following is a list of the species examined and of the alkaloids found. The figures in brackets are percentages of total alkaloids. 

Hydrangea umbellata Rheder (Saxifragaceae). A Chinese anti-malarial drug said to contain several crystalline alkaloids. (Jang, Fu, Huang, Wang, Nature, 1948, 161, 401.)... 

In the course of the intensive campaign carried on in the United States of America during the war for the discovery of effective anti-malarial drugs, a team of workers made anti-malarial tests on 600 different plants belonging to 123 families of phanerogams and three families of cryptogams, and it is recorded that the suppressive activity shown by some of these plants appeared to be associated with alkaloidal fractions of their extracts. 

Isonitriles are stable, often naturally occurring, compounds that contain a divalent carbon. An example is axisonitrile-3, which can be isolated from a species of sponge and possesses anti-malarial activity. Write a resonance form for axisonitrile-3 that satisfies the octet rule. Don t forget to include formal charges. 

Malaria is transmitted from person to person by a certain species of the Anopheles mosquito. The four different protozoans causing malaria are Plasmodium falciparum, P. malariae, P. ovale, and P. vivax. Drugp used to treat or prevent malaria are called anti malarial drags. Three antimalarial drugs are discussed in the chapter chloroquine, doxycycline, and quinine sulfate. Other examples of antimalarial drugs in use today are listed in the Summary Drug Table Antimalarial Drugs. 

Among the many anti-malarial drugs tried in the 1940s and 1950s was (3) (cf p 104). The better C-N... 

CloHi3NO i5-Amlno-ether Anti-malarial (3) W124... 

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