Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives.

Point mutations in dihydrofolate reductase (DHFR), especially the double mutant variant (A16V + S108T), led to ineffective inhibiting by cycloguanil (Cyc). Cycloguanil derivatives showed good inhibiting properties against wild-type and mutant DHFR with an inhibition constant as low as the nanomolar level. However, there have been no reports on the stereochemistry of the compounds, and this is important because the pure enantiomeric form of a chiral drug can exert desirable, as well as non-desirable responses on the body or both.