TABLE 1

In vitro antiplasmodial activity, physicochemical properties, and in vitro microsomal metabolism data of sulfoxide and sulfone

ParameteraSulfoxideSulfone
PfNF54 IC50 (nM)15.9 ± 1.08.4 ± 1.7
PfK1 IC50 (nM)14.0 ± 2.310 ± 1.9
Pf3D70087/N9 IC50 (nM)11.8 ± 1.19.6 ± 0.8
Solubility (pH 7.4) (µM)7025
LogD2.12.5
PAMPA−4.1−4.2
MLM EH0.3<0.1
HLM EH0.2<0.1
  • a LogD, the log of the distribution coefficient (D) for molecules partitioned between octanol and water at pH 7.4; PAMPA, parallel artificial membrane permeability assay; MLM EH, mouse liver microsome extraction coefficient; HLM EH, human liver microsome extraction coefficient.