title: Benzofuranyl 3,5-bis-polyamine derivatives as time-dependent inhibitors of trypanothione reductase.
abstract: The synthesis and evaluation of 3,5-disubstituted benzofuran derivatives as time-dependent inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the bis-4-methyl-piperazin-1-yl-propylacrylamide derivative 4 displayed time-dependent activity. The kinetics of time dependent inactivation of trypanothione reductase by 1 and 4 have been determined and are compared and discussed herein.
authors.affiliation: Division of Biological Chemistry & Molecular Microbiology, Faculty of Life Sciences, Carnelley Building, University of Dundee, DD1 4HN, Dundee, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hamilton
authors.forename: Ahilan
authors.initials: A
authors.lastname: Saravanamuthu
authors.forename: Alan H
authors.initials: AH
authors.lastname: Fairlamb
authors.forename: Ian M
authors.initials: IM
authors.lastname: Eggleston
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects* / Q000378:metabolism; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014345:Trypanosoma / Q000201:enzymology
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; D011073:Polyamines; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase