This model involves the inhibition of hemozoin biocrystallization in the heme detoxification pathway, which facilitates the aggregation of cytotoxic heme. Free cytotoxic heme accumulates in the parasites, causing their deaths. Quinine may target the malaria purine nucleoside phosphorylase enzyme. Chemistry
The UV absorption of quinine peaks around 350 nm (in UVA). Fluorescent emission peaks at around 460 nm (bright blue/cyan hue). Quinine is highly fluorescent (quantum yield ~0.58) in 0.1 M sulfuric acid solution. Synthesis
Cinchona trees remain the only economically practical source of quinine. However, under wartime pressure during World War II, research towards its synthetic production was undertaken. A formal chemical synthesis was accomplished in 1944 by American chemists R.B. Woodward and W.E. Doering. Since then, several more efficient quinine total syntheses have been achieved, but none of them can compete in economic terms with isolation of the alkaloid from natural sources. The first synthetic organic dye, mauveine, was discovered by William Henry Perkin in 1856 while he was attempting to synthesize quinine. Biosynthesis
In the first step of quinine biosynthesis, the enzyme strictosidine synthase catalyzes a stereoselective Pictet–Spengler reaction between tryptamine and secologanin to yield strictosidine. Suitable modification of strictosidine leads to an aldehyde. Hydrolysis and decarboxylation would initially remove one carbon from the iridoid portion and produce corynantheal. Then the tryptamine side-chain were cleaved adjacent to the nitrogen, and this nitrogen was then bonded to the acetaldehyde function to yield cinchonaminal. Ring opening in the indole heterocyclic ring could generate new amine and keto functions.
Treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease. Uses
Medical
As of 2006, quinine is no longer recommended by the World Health Organization (WHO) as a first-line treatment for malaria, because there are other substances that are equally effective with fewer side effects. They recommend that it be used only when artemisinins are not available. Quinine is also used to treat lupus and arthritis. Quinine was frequently prescribed as an off-label treatment for leg cramps at night, but this has become less common due to a warning from the US Food and Drug Administration (FDA) that such practice is associated with life-threatening side effects. Quinine can also act as a competitive inhibitor of monoamine oxidase (MAO), an enzyme that removes neurotransmitters from the brain. As an MAO inhibitor, it has potential to serve as a treatment for individuals with psychological disorders similar to antidepressants that inhibit MAO. Available forms
Quinine is a basic amine and is usually provided as a salt. Various existing preparations include the hydrochloride, dihydrochloride, sulfate, bisulfate and gluconate. In the United States, quinine sulfate is commercially available in 324-mg tablets under the brand name Qualaquin. All quinine salts may be given orally or intravenously (IV); quinine gluconate may also be given intramuscularly (IM) or rectally (PR). The main problem with the rectal route is that the dose can be expelled before it is completely absorbed; in practice, this is corrected by giving a further half dose.