Eugene A. Coats

QSAR OF BACTERIAL FOLATE-SYNTHESIS INHIBITORS

Abstract De novo synthesis of dihydrofolate is unique for several microorganisms, parasites and plants. The synthetic pathway of dihydrofolate is therefore a suitable target for specific inhibitors. To optimize inhibitors for specific biological systems, detailed quantitative structure-activity relationships (QSAR) have been derived for a series of sulfones, sulfonamides, and pyrimidines of the trimethoprim type using whole cell bacteria and cell-free folate synthesizing enzyme extracts from Escherichia coli, Mycobacterium lufu and Mycobacterium smegmatis (ATCC 607). The correlation equations obtained show different degrees of dependence upon electronic factors of the substituents for binding to the target proteins and different influences of cell-wall permeation processes.