Properties of Brodimoprim as an Inhibitor of Dihydrofolate Reductases

Abstract

Based on both IC₅₀ and K_i values, brodimoprim (BDP) was often found to be two- to threefold more effective than trimethoprim (TMP) against a great variety of different bacterial dihydrofolate reductases (DHFR). In all cases BDP was found to be a reversible, tight-binding inhibitor. The higher affinity for enzymes relatively insensitive to TMP, like those of Nocardia, which is paralleled by higher in vitro activity, may be therapeutically useful. BDP also often inhibited plasmid-coded, TMP-resistant DHFRs, as well as altered chromosomal TMP-resistant DHFRs at lower concentrations than TMP did, this property, however, being therapeutically irrelevant. A higher affinity was also observed for eucaryotic DHFRs, the specificity, however, remaining similar to that of TMP.