Mechanism of action of the folate blocker diaminodiphenylsulfone (dapsone, DDS) studied in E. coli cell-free enzyme extracts in comparison to sulfonamides (SA).

The antibacterial activity of DDS has been studied in whole cell (E. coli), cell-free folate synthesizing enzyme extracts and compared to effects obtained for sulfonamides (SA). It is shown that DDS acts as a synthetase inhibitor in the folate synthesizing enzyme system. DDS reacts with the substrate 7,8-dihydro-6-hydroxymethylpterinopyrophosphate to form a 7,8-dihydropteroic acid analog. Bacterial growth kinetic studies were performed to test for possible synergistic activity of the analog in combination with DDS. Possible reasons for the extremely large inhibitory power of DDS against M. leprae are discussed.