Quinoline antimalarial drugs

Malaria is still one of the world s most devastating infectious diseases. An estimated 270 million people are affected by the parasite every year, and close to 2 million children die. The most deadly species, Plasmodium falciparum, has become widely resistant to most of the available antimalarial drugs such as quinolines. 

Malaria parasite has developed resistance to many of these so-called quinoline antimalarials rendering them completely obsolete. This situation has forced the use of combination regimens that consists of a mixture of two or more antimalarial active ingredients this approach has proven to work better than monotherapies, but often is only a temporary soulu-tion. Nevertheless, quinine remains a very effective drug, with only few treatment failures or resistance reported around the globe. 

Quinidine (6) and quinine (7) are diastereomeric quinoline alkaloids obtained from Cinchona spp. Quinidine (6) is included in many pharmacopeias for its antiarrhythmic effects.Quinine was the first antimalarial drug and served as an effective remedy for this deadly infectious disease in colonial times, making European settlement in many tropical and subtropical parts of the world possible.Owing to the development of resistance to synthetic antimalarials, quinine is still reverted to some extent for this... 

Halofantrine was an important antimalarial drug. It is now infrequently used because of worldwide strain resistance phenomena. Tafenoquine is a new 8-amino-quinoline currently in clinical trials (Phase III) (Figure 8.26). ... 

Quinine Quinine, molecular formula C20H24N2O2, is a white crystalline quinoline alkaloid, isolated from Cinchona hark Cinchona succirubra), and is well known as an antimalarial drug. Quinine is extremely bitter, and also possesses antipyretic, analgesic and anti-inflammatory properties. While quinine is stiU the drug of choice for the treatment of Falciparum malaria, it can be also used to treat nocturnal leg cramps and arthritis. Quinine is an extremely basic compound, and is available in its salt forms, e.g. sulphate, hydrochloride and gluconate. 

Vlakhov R, Parushev S, Vlakhov I, Nickel P, Snatzke G (1990) Synthesis of some new quinoline derivatives - potential antimalarial drugs. Pure Appl Chem 62 1303-1306 Madrid PB, Sherrill J, Liou AP, Weisman JL, DeRisi JL, Kipling GR (2005) Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities. Bioorg Med Chem Lett 15 1015-1018... 

Cinchona species (Rubiaceae) are sources of quinine and quinidine, containing a quinoline nucleus and derived through the extensive elaboration of strictosidine (Fig. 42). The intriguing history of the antimalarial quinine and its role in world politics over the past 350 years are legendary. It is frequently the only antimalarial drug to which patients are not resistant. Its widest use, however, is in the beverage industry in tonic water. Quinidine, an isomer of quinine, is used to treat cardiac arrythmias. 

OR Idowu, JO Peggins, TG Brewer, C Kelley. Metabolism of a candidate 8-amino-quinoline antimalarial agent, WR 238605, by rat liver microsomes. Drug Metab Dispos 23 1, 1995. 

Dimethoxy-2(lH)-quinolines (235), which are key intermediates for the synthesis of antimalarial drugs, have been prepared in poor to moderate yields by intramolecular Wittig reaction of the salts (234). A combination of Wittig olefination and Claisen rearrangement of (2-hydroxy-4-prenyloxy)phenyl carbonyl compounds (236) has been used in a one-pot synthesis of 2, 3, 3 -trimethyl-2, 3 -dihydroangelicins (237). ... 

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