Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents.
Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with Ki values < 5 microM are described). The most effective inhibitor studied was compound 12 with a Ki value of 0.151 microM. Six of the compounds described are also effective trypanocides with IC50 values < 1 microM.
Li
Z
Z
Department of Chemistry, Indiana State University, Terre Haute 47809, USA.
Fennie
M W
MW
Ganem
B
B
Hancock
M T
MT
Kobaslija
M
M
Rattendi
D
D
Bacchi
C J
CJ
O'Sullivan
M C
MC
D000818:Animals; D001667:Binding, Competitive; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013095:Spermidine / Q000031:analogs & derivatives; D013096:Spermine / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000201:enzymology; D014349:Trypanosoma cruzi / Q000201:enzymology
D004791:Enzyme Inhibitors; D011073:Polyamines; D014344:Trypanocidal Agents; D013096:Spermine; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D013095:Spermidine