title: Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents.
abstract: 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.
authors.affiliation: Department of Chemistry, Indiana State University, Terre Haute 47809, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: M W
authors.initials: MW
authors.lastname: Fennie
authors.forename: B
authors.initials: B
authors.lastname: Ganem
authors.forename: M T
authors.initials: MT
authors.lastname: Hancock
authors.forename: M
authors.initials: M
authors.lastname: Kobaslija
authors.forename: D
authors.initials: D
authors.lastname: Rattendi
authors.forename: C J
authors.initials: CJ
authors.lastname: Bacchi
authors.forename: M C
authors.initials: MC
authors.lastname: O'Sullivan
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D011073:Polyamines; D014344:Trypanocidal Agents; D013096:Spermine; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D013095:Spermidine