Sulfa drug

From Free net encyclopedia

Sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide group. In bacteria, sulfa drugs act as competitive inhibitors of para-Aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. This reaction is necessary in these organisms for the synthesis of folic acid.

1 History
2 Preparation
3 See also
4 External links

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History

The first sulfonamide was trade named prontosil, which is a prodrug. The first experiments with prontosil began in 1932 by the German chemist Gerhard Domagk, and the results were published in 1935 (after his employer, IG Farben, had obtained a patent on the compound). Prontosil was a red azo dye, and in mice had a protective action against streptococci. It had no effect in the test tube, and only exerted an antibacterial effect in the live animal itself. The drug is connected with an azo bond, which is a N=N bond. This bond is easily broken in the GI tract to release the active drug sulfanilamide. And, with war on the horizon, there was interest among the Allies to break the German patent.

Soon it was discovered (1936) that prontosil's active agent was a smaller, more effective compound known as sulfanilamide:

Image:Sulfanilamide-skeletal.png

Sulfanilamide had a central role in preventing infection during World War II. American soldiers were issued a first aid kit containing sulfa powder and were told to sprinkle sulfa on any open wound. During the years 1942 to 1943, Nazi doctors conducted sulfanilamide experiments on prisoners in Ravensbrück.

An inadvertently toxic preparation of sulfanilamide also had a central influence on the US Food and Drug Administration. A preparation called Elixir Sulfanilamide contained diethylene glycol as a solvent, which is toxic. This preparation killed over one hundred people, mostly children, and led to the passage of the 1938 Food, Drug, and Cosmetic Act.

The Sulfanilamide compound is more active the protonated form, which in case of the acid works better in a basic enivorment. The solubility of the drug is very low and sometimes can crystalize in the kidneys, due to its first pka of around 10. This is a very painful experience so patients are told to take the medication with copious amounts of water. Newer compounds have a pka of around 5-6 so the problem is avoided.

Many thousands of permutations of the sulfanilamide structure have been created since its discovery (by one account, over 5400 permutations by 1945), usually by the substitution of another functional group for a single amide hydrogen.

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