Optimising inhibitors of trypanothione reductase using solid-phase chemistry.
A series of inhibitors of the enzyme trypanothione reductase has been identified using directed solid-phase chemistry. The compounds were based on a series of polyamine scaffolds and used the natural product kukoamine A as the lead structure. A compound with a Ki of 76 nM was identified, although somewhat surprisingly the compound appeared to be noncompetitive in nature.
Chitkul
B
B
Department of Chemistry, University of Southamton, UK.
Bradley
M
M
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D007700:Kinetics; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011073:Polyamines; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase