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Development of New and Selective Trypanosoma cruzi trans‐Sialidase Inhibitors from Sulfonamide Chalcones and Their Derivatives
Author(s) -
Kim Jin Hyo,
Ryu Hyung Won,
Shim Jae Hoon,
Park Ki Hun,
Withers Stephen G.
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900108
Subject(s) - sulfonamide , chalcone , chemistry , catechol , sialidase , trypanosoma cruzi , stereochemistry , non competitive inhibition , lactose , hydrolysis , enzyme , biochemistry , neuraminidase , parasite hosting , world wide web , computer science
A series of sulfonamide‐containing hydroxylated chalcone ( 4 – 7 ) and quinolinone ( 8 , 9 ) derivatives was synthesised and tested for inhibition of the trans‐sialidase from Trypanosoma cruzi (TcTS). IC 50 values for these inhibitors ranged from 0.6 to 7.3 μ M , with the dihydroxylated (catechol) derivatives being the tightest binders. Full kinetic analyses of inhibition were performed for these catechol derivatives, both for the transglycosylation reaction in the presence of lactose and for the hydrolysis reaction in its absence. Competitive inhibition was seen in each case with K i values for 5 , 7 and 9 of 2.0, 2.2 and 0.2 μ M , respectively, in the absence of lactose, and 4.6, 3.7 and 0.4 μ M in its presence. None of the compounds tested showed any significant inhibition of the human sialidase Neu2, at concentrations up to 200 μ M .