Malaria, drugs for

The disadvantage in war periods of relying on a single source of supply for an essential commodity became evident when Java was invaded by the Japanese in March 1942, the world being thereby deprived of about 90 per cent, of its customary supply of cinchona bark. Quinine was ther still considered an indispensable drug for the treatment of malaria an<3 its use had to be restricted to that purpose stocks of quinidine wew similarly reserved for use in cardiac disease, In efforts to deal with th<... 

The selectivity of the cyclization using enamino-esters 18-20 derived from m-halogenated anilines 14-16, provided mixtures of 5- and 7-substituted quinolines. In all of these cases, the cyclization gave either equal amounts of the 5- and 7- isomers or in the case of m-iodoaniline, about a 1 2 ratio was observed. During the time of these publications, it was the desire of the authors to obtain the 7-substituted quinolines, which were potential drugs for the treatment of malaria. 

Schirmer, R. H., Muller, J. G and Krauth-Siegel, R. L., Disulfide-reductase inhibitors as chemotherapeutic agents The design of drugs for trypanosomiasis and malaria. Angew, Chem., Int. Ed. Engl. 34,141-154 (1995). 

It has been shown that a few sulfones and sulfonamides may be of interest as drugs for treating malaria. Experimental research uncovered the pronounced synergism between sulfonamides and chloroguanide and pyrimethamine. 

Examples include The Institute for One World Health, The Drugs for Neglected Diseases Initiative, and The Medicines for Malaria Venture. 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

Thus far no major adverse effects have been reported for artemisinin and its derivatives. Although neurotoxicity can occur in animals, it has never been reported in humans. However, subclinical cumulative neurotoxicity could occur with each treatment course for separate episodes of malaria. This possible risk prohibits the use of artemisinin drugs for malaria prophylaxis. 

Antimalarials Mefloquine is a major drug for malaria, in particular, for chloroquine-resistant malaria." However, some cases of neuropsychiatric adverse events and the apparition of resistance tend to limit its use. Metabolism into inactive and phototoxic 1 -7/-2-oxoquinoline is blocked by the presence of the CF3 group." Instead of performing the resolution of enantiomers at the end of the synthesis," the asymmetric reduction of the carbonyl group in the presence of ruthenium catalyst and a chiral diphosphine provided mefloquine with an excellent enantiomeric excess (Figure 8.25). °... 

Malaria in man is caused by several species of protozoan parasites known as plasmodia. The oldest effective drug for the treatment of this disease is indisputably quinine (13), a... 

Mefloquine is effective therapy for many chloroquine-resistant strains of P falciparum and against other species. Although toxicity is a concern, mefloquine is one of the recommended chemoprophylactic drugs for use in most malaria-endemic regions with chloroquine-resistant strains. 

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