Quinine antimalarial agent

Quinine hydrochloride [Fig. 22(c)], an antimalarial agent, acts primarily as a schizonto-cide, affecting sporozoites or preerythrocytic forms of malarial parasites [43]. Figure 23(c) shows potential oscillation with ImM quinine hydrochloride [21]. Fb.sds became very... 

The first synthetic quinoline antimalarial agent interestingly carried the basic side chains at the 8 rather than the 4 position, as in quinine, lending further credence to the... 

Clinical Use. Mefloquine (Lariam) has emerged as one of the most important antimalarial agents.61 This drug is especially important in the prevention and treatment of malaria that is resistant to traditional antimalarial drugs such as chloroquine and quinine.50 Mefloquine is often the drug of choice for antimalarial prophylaxis, especially in areas of the world where chloroquine-resistant strains of malaria are common.23 Mefloquine can be used alone, but combining this... 

Quinidine, cinchonine, and cinchonidine also have antimalarial properties, but these alkaloids are not as effective as quinine. The cardiac effect makes quinidine unsuitable as an antimalarial. However, mixtures of total Cinchona alkaloids, even though low in quinine content, are acceptable antimalarial agents. This mixture, termed totaquine, has served as a substitute for quinine during shortages. Quinine-related alkaloids, especially quinidine, are also found in the bark of Remija pendunculata (Rubiaceae). 

Following the development of synthetic antimalarial agents, such as chloroquine and mefloquine, the use of Cinchona alkaloid quinine declined. However, with the emergence of chloroquine-resistant and multiple-drug-resistant strains of malarial parasites, its use has become firmly reestablished. Quinine is the drug of choice for severe chloroquine-resistant malaria due to Plasmodium falciparum. In the U.S., the related alkaloid quinidine is recommended because of its wide availability and use as an antiarrhythmic agent. In many clinics in the tropics, quinine is the only effective treatment for severe malaria unfortunately, decreasing sensitivity of P. falciparum to quinine has already been reported from Southeast Asia. 

The medicinal use of quinine, an antimalarial agent, dates back over 350 years. Quinine is the chief alkaloid of cinchona, the bark of the South American cinchona tree, otherwise known as Peruvian bark, Jesuit s bark, or Cardinal s bark. In 1633, an Augustinian monk named Calan-cha of Lima, Peru, first wrote that a powder of cinchona given as a beverage, cures the fevers and tertians. By 1640, cinchona was used to treat fevers in Europe, a fact first mentioned in the European medical literature in 1643. The Jesuit fathers were the main importers and distributors of cinchona in Europe, hence the name Jesuit s bark. Cinchona also was called Cardinal s bark because it was sponsored in Rome by the eminent philosopher, Cardinal de Lugo. 

FIGURE 22.3 The structure of quinine and other antimalarial agents. 

Qunidine and quinine Antiarry thmic/antimalarial agent Cinchona pubescens Quinine tree... 

Quinine The antimalarial agent quinine is derived from the bark of the cinchona tree along with several other alkaloids and salicylate (aspirin). Many of these agents produce similar toxic features (cinchon-ism) in patients with excessive intake, but only quinine produces blindness. Cinchonism consists of abdominal pain and vomiting, ringing in the ears (tinnitus), and confusion. Visual loss after quinine overdose is due to direct retinal toxicity, although until recently it was believed to be due to spasm of the arterial blood supply to the retina. Treatment is difficult, but limited evidence suggests charcoal hemoperfusion may be beneficial (hemoperfusion is similar to hemodialysis, except in place of a semi-permeable membrane to filter the toxin from the blood, charcoal is used to bind the toxin). 

The highly effective antimalarial agent chloroquine—a drug developed from quinine—can attack the malarial parasite by blocking DNA transcription as part of its action. Once again a flat heteroaromatic structure is present which can intercalate DNA (Fig. 6.8). 

Hybridisation takes place between amole of acetylsalicylic acid (i.e., aspirin) and quinine (i.e., a potent antimalarial agent) to lose a mole of water and the resulting hyberdised product potentiates the antimalarial activity along with substantial antipyretic—analgesic activity. 

Later, the same group developed a modification to the original procedure and applied it to the synthesis of valuable intermediates en-route to chloroquine and antimalarial agents quinine and its derivatives (04T3017, 05JOM5398). As an extension of the method, the authors used not only... 

Alkaloids are naturally occurring amines that are powerfully active biologically. They are among the most useful medicinal agents known. The painkiller morphine and the antimalarial agent quinine are typical examples. At the same time, some of the... 

Cinchona succirubra (Rubiaceae) is a tall tree that grows wild in the Andes of Peru and Brazil. It is cultivated in Java and Sumatra. The bark contains 5%-8% total alkaloids. The major alkaloid, quinine, has been used as an antimalarial agent. Cinchonidine, cinchonine, and quinidine have also been obtained. 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

So, in a way, it is with quinine, known (29) since antiquity as a potent antimalarial. For chemists, the use of quinicine in 1854 in the first resolution of a racemate (1,3) marks a milestone Stereochemistry as we know it today made its debut in that year. In resolutions, quinine and its diastereomers proved to be safe to handle (compare the extreme toxicity of brucine or strychnine with that of quinine), versatile in their applications, and available in reasonably pure form. Little wonder that even today, 131 years after its first use as a resolving agent, quinine (and brucine) continues to be the chemical of choice when one is attempting a new resolution of a racemic acid (90). 

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