Sulfa drugs were the first synthetic drugs with widespread antibiotic activity to be put into clinical use. In the 1930s German chemists observed that certain dyes used to stain bacteria stopped microbial growth. Gerhard Domagk, a pathologist at I. G. Farbenindustrie, performed a series of experiments on mice infected with streptococcus bacteria and observed that mice injected with an orange-red dye called Prontosil survived bacterial infection. Prontosil is an azo dye that had not shown antibacterial activity during earlier in vitro tests. However, in vivo , the dye is transformed into sulfanilamide, a compound with antimicrobial activity (see Figure 1). Domagk had such faith in Prontosil's anti-infectious properties that he is reported to have injected the dye into his daughter when she had septicemia. In 1939 Domagk was awarded the Nobel Prize in physiology or medicine for his discovery.
Once sulfanilamide was recognized as an active antimicrobial agent, scientists synthesized thousands of sulfonamides to test for bactericidal activity. It was later realized that sulfonamides do not actually kill bacteria; they interfere with bacterial growth and replication. Sulfa drugs are bacteriostatic. They inhibit an enzyme necessary for the biosynthesis of folic acid in bacteria. Folic acid is necessary for the biosynthesis of thymine and the purine bases, the building blocks of DNA . Bacteria that are sensitive to sulfa drugs are unable to acquire folic acid from their environment and, in the presence of sulfonamides, are unable to synthesize the folic acid essential for cell growth and multiplication. Sulfonamides do not harm their human hosts, however, because, unlike susceptible bacteria, humans acquire folic acid from their diet and lack the enzyme necessary for synthesizing folic acid.
American Chemical Society (2000). The Pharmaceutical Century: Ten Decades of Drug Discovery. Washington, DC: ACS.
Williams, David A., and Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry, 5th edition. Baltimore: Lippincott Williams & Wilkins.
Wolff, Manfred E., ed. (2003). Burger's Medicinal Chemistry and Drug Discovery, 6th edition. New York: Wiley.
"The Nobel Prize in Physiology or Medicine 1939." Nobel e-Museum. Available from http://www.nobel.se .