Quinine antimalarial

QUININE ANTIMALARIALS - MEFLOQUINE Risk of seizures Additive effect Warn patients of the risk patients should be advised to avoid driving while taking these drugs in combination... 

A number of early medicines, including morphine (analgesic) and quinine (antimalarial), were isolated from plants. Over the years the search for... 

Quinine Antimalarial Cinchona bark (Chinchona officinaiis)... 

The heme coordination polymer which results from the heme polymerase activity of the plasmodium parasite is an insoluble crystalline solid with prc ionate interheme links. How the quinine antimalarials inhibit heme polymerase and how this enzyme is associated with jS-hematin remain important, albeit poorly understood, aspects of this biochemistry. Furthermore, heme detoxification by malaria is the only currently recognized example of iron excretion. The homeostasis of iron is usually srictly controlled, and excess is usually stored in ferritin for subsequent... 

Although quinine is a favored antimalarial for parenteral adrninistration, it is nevertheless hazardous by this route. Quinidine (64), has been shown to be even more effective in combatting the disease (Table 8). However, it has undesirable cardiac side effects that reduce its suitabiHty as an antimalarial. 

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. 

The antimalarial properties attributed to preparations from Dichroa febrifuga by the Chinese were confirmed about 1944 and two alkaloids, febrifugine (999) and isofebrifugine (1000), were isolated eventually. After difficult structural elucidations, syntheses of ( )-febrifugine followed it proved to be half as active as the natural material, itself far better than quinine, but the therapeutic index was disappointingly low (67HC(24-l)490). 

The oldest effective drug for the treatment of this disease is indisputably quinine. Although the antipyretic activity of cinchona bark was known to the Incas, it remained for the Jesuit missionaries to uncover its antimalarial properties in the early seventeenth century. The advance of organic chemistry led to the isolation and identification of the alkaloid, quinine, as the active compound at the turn of this century. The emerging clinical importance of this drug led up to the establishment of cinchona plantations in the Dutch East Indies. This very circum-... 

Quinine, an arylaminoalcohol, was the first antimalarial known to the Western world. It was originally produced from the bark of the cinchona tree and distributed as a powdery substance, which became... 

Pinworm is a helminHi infection that is universally common most oHier helminth infections are predomi-lianHy found in countries or areas of the world that lack proper sanitary facilities. Malaria is rare in the United States, but it is sometimes seen in individuals who have traveled to or lived in areas where this disease is a healtii problem. The first antimalarial drug, quinine, is derived from the bark of the cinchona tree. Amebiasis is seen Hiroughout the world, but it is less common in developed countries where sanitary facilities prevent Hie spread of the causative organism. 

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. 

Cinchona alkaloids have been used as drugs for the treatment of several diseases. Quinine is very popular as an antimalarial drug against the erythrocyte stage of the parasite [34]. Recently, Shibuya et al. (2003) reported the microbial transformation of four Cinchona alkaloids (quinine, quini-dine, cinchonidine, and cinchonine) by endophytic fungi isolated from Cin-... 

The next milestone in the development of organic synthesis was the preparation of the first synthetic dye, mauveine (aniline purple) by Perkin in 1856 Perkin, 1856, 1862). This is generally regarded as the first industrial organic synthesis. It is also a remarkable example of serendipity. Perkin s goal was the synthesis of the antimalarial drug quinine by oxidation of N-allyl toluidine (Fig. 2.4). 

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 foundation of the synthetic dye industry is universally attributed to William Henry Perkin on account of his discovery in 1856 of a purple dye which he originally gave the name Aniline Purple, but which was later to become known as Mauveine. Perkin was a young enthusiastic British organic chemist who was carrying out research aimed not initially at synthetic dyes but rather at developing a synthetic route to quinine, the antimalarial drug. His objective in one particular set of experiments was... 

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). 

All the material world is formed of mixtures, aggregates or more complex combinations of pure substances. For example, it is well known that the bark of the Cinchona tree Cinchona calisaya) shows a remarkable antimalarial activity, which is due, not to the bark as such, but to some "pure substance" which forms an integral part of it. In 1820, the French pharmacists Pelletier and Caventou isolated the active principle of the Cinchona bark, which they called quinine, as a pure, crystalline substance, m.p. 177 °C (dec), -169°, and assigned an elemental... 

It must not be forgotten that the concept of pure substance, referred to earlier, is very rigorous and must take into account, not just the constitution and relative configuration of a molecule, but also the absolute configuration of each chiral center that may present. For example, again in relation to quinine (i), quinidine (2) is also known and the only difference between the two molecules is the disposition in space of the groups bonded to C(8). Nevertheless 2 is a different molecule and shows no antimalarial activity. In addition, only one enantiomer of quinine (1), the laevorotatory, corresponds to the natural compound and manifests the specific physiological properties associated with this substance. 

Initially approved in the 1930s as antimalarial drug, quinacrine (2) became one of the first potential substitutes to quinine. The total synthesis of quinacrine would be achieved in 1931 by German scientists at Bayer,and it would be subsequently marketed as Mepacrine or Atebrine. However, quinacrine would soon be replaced by another synthetic and more efficient antimalarial drug, chloroquine (3). 

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