Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain.
A new family of potent N-alkoxyvinylsulfonamide inhibitors of cruzain have been developed. Inhibitor 13 has a second order inactivation rate constant of 6,480,000s(-1)M(-1) versus cruzain, and is also highly effective against Trypanosoma cruzi trypomastigotes in a tissue culture assay.
Roush
W R
WR
Department of Chemistry, University of Michigan, Ann Arbor, 48109, USA. roush@umich.edu
Cheng
J
J
Knapp-Reed
B
B
Alvarez-Hernandez
A
A
McKerrow
J H
JH
Hansell
E
E
Engel
J C
JC
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D013449:Sulfonamides; D014344:Trypanocidal Agents; C440389:vinyl sulfonamide; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi