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Wednesday, July 25, 2007

Quinine and Malaria

Monday's Molecule #36 was quinine, an alkaloid isolated from the bark of Chichona, or quinine tree [Cinchona pubescens]. The tree originally grew only on the eastern slopes of the Andes in South America where the bark was widely used by the natives to prevent malaria and other diseases. Following the discovery of its amazing properties by Europeans, it was transported to other tropical parts of the world.

Quinine works by attacking the parasite that causes malaria. This protozoan parasite, Plasmodium falciparum, feeds on red blood cells. It can easily digest hemoglobin but can't handle the heme groups that are released when the protein is degraded. These heme groups are toxic to the parasite so they are stored in an inactive form inside a membrane-bound organelle called a digestive vacuole. Quinine interferes with this storage causing the hemes to remain free where they poison the cell. The exact mechanism is unknown but it is known that quinine has to enter the vacuole in order to be effective. The most likely mechanism is quinine binding to the heme molecule to prevent its conversion to the inactive form celled haemozoin.

Resistance to quinine and related compounds is usually due to mutations in transporter proteins that are found in the membranes of the digestive vacuole. The mutations prevent the accumulation of quinine in the vacuole.

Quinine is present in tonic water that was widely consumed in the last century to ward off malaria. The quinine imparts a bitter taste to tonic water so, as the story goes, British tourists used to dilute it with gin to hide the taste. The gin & tonic mixture became quire popular.

As a matter of fact, quinine is still present in modern bottles of tonic water. This can be easily demonstrated by shining ultraviolet light on a bottle of tonic water since quinine is fluorescent (left). To see how much quinine you get in a gin & tonic see [The Half-Decent Phamaceutical Chemistry Blog].

Quinine was synthesized after World War II but it isn't economical to make the drug and the only effective source is the bark of Chichona. However, a more effective drug called chloroquine (below) became widely available after World War II and it has mostly replaced quinine as the preferred drug against malaria.