Analysis of 6-(2,2-Dichloroacetamido)chrysene interaction with the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi.
Selective inhibition is needed for drugs targeting the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi, etiologic agent of Chagas' disease. 6-(2,2-Dichloroacetamido)chrysene, was shown herein to be a selective inhibitor of the trypanosomal enzyme. SAR analysis revealed that the 6-amido moiety was essential, but the dichloroaceto moiety was not essential for achieving the low K(i) for this inhibitor. Understanding the molecular basis for these interactions could facilitate the design of selective inhibitors without a chrysene moiety.
Medrano
Francisco J
FJ
Laboratory of Molecular Parasitology & Drug Design, Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269-3044, USA.
Wenck
Mary A
MA
Engel
Juan C
JC
Craig
Sydney P
SP
D000818:Animals; D002911:Chrysenes / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011485:Protein Binding; D014344:Trypanocidal Agents / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000737:chemistry*
C475436:6-(2,2-dichloroacetamido)chrysene; D002911:Chrysenes; D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D007041:Hypoxanthine Phosphoribosyltransferase