Triazole inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase

摘要: Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. This protozoan parasite cannot salvage guanine or guanosine therefore relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for biosynthesis of nucleotides hence survival. Because C. IMPDH highly divergent from the host counterpart, selective inhibitors could potentially be used to treat cryptosporidiosis with minimal effects its mammalian host. A series 1,2,3-triazole containing ether CpIMPDH are described. structure-activity relationship study revealed that a small alkyl group alpha-position was required, (R)-enantiomer significantly more active than (S)-enantiomer. Electron-withdrawing groups in 3- and/or 4-positions pendent phenyl ring were best, conversion quinoline quinoline-N-oxides retained inhibitory activity both presence absence bovine serum albumin. The provide new tools elucidating role may serve as therapeutics treating cryptosporidiosis.