[Inhibitors of folic acid metabolism (author's transl)].

In contrast to antibiotic research, the study of folic acid metabolism and folic acid antagonists is conducted in the classical tradition of chemotherapy established by Paul Ehrlich. The elucidation of the mechanism of action of sulphonamides created an important prerequisite for the understanding of the biosynthesis of folic acid. The synthesis of inhibitors of dihydrofolate-reductase was guided on the one hand by the structure of dihydrofolate itself, and on the other hand by the fact that this substnce is essential for the growth of certain bacteria. Both approaches led to the synthesis of compounds which were effective and could be used therapeutically. The mechanism of selectivity of folic acid antagonists is described. A short account of the biochemical and genetic basis of resistance to folic acid antagonists is also given. The study of folic acid metabolism and folic acid antagonists provides a good example of the successful interaction of mechanistically inspired biochemical and chemical methods on the one hand, and an empirical approach characterised by the study of more complex biological phenomena on the other hand.