Pyrimethamine and sulfadoxine

Pyrimethamine (PYR) was developed in the early 1950s by Gertrude Elion and George Hitchings and is now sold under the trade name Daraprim™ [49]. The development of pyrimethamine was a part of the efforts that won Elion, Hitchings and Black the joint Nobel Prize in Physiology or Medicine in 1988 for “their discoveries of important principles for drug treatment” [50]. Sulfadoxine was developed in the early 1960s [51]. It is no longer used as a preventative drug due to high levels of resistance. The combination of pyrimethamine and sulfadoxine was approved for use for the treatment of malaria in 1981 and is now commonly sold under the trade name Fansidar®. Both drugs are known to target the parasite folate biosynthesis pathway [52]. Pyrimethamine inhibits dihydrofolate reductase, while sulfadoxine inhibits dihydropteroate synthetase.