Jw. Benbow et al., SYNTHESIS AND EVALUATION OF DINITROANILINES FOR TREATMENT OF CRYPTOSPORIDIOSIS, Antimicrobial agents and chemotherapy, 42(2), 1998, pp. 339-343
The efficacy of a series of dinitroaniline herbicide derivatives for t
he treatment of Cryptosporidium parvum infections has been studied. Th
e lead compounds oryzalin (compound 1) and trifluralin (compound 2) ha
ve low water solubility (< 3 ppm) which was alleged to be a major cont
ributor to their poor pharmacokinetic availability. Derivatives of com
pounds 1 and 2 were synthesized. In these derivatives the functionalit
y at the C-1 amine position or the C-4 position was substituted with g
roups with various hydrophilicities to determine if a direct relation
existed between water solubility and overall activity. The chlorinated
precursors of these derivatives were also examined and were found to
be less active in the C. parvum assays, a result in direct contrast to
earlier work with Leishmania. Enhanced water solubility alone did not
overcome the drug availability problem; however, several candidates w
ith similar activities but with toxicities lower than those of the lea
d compounds were produced.