Indolizine 1-sulfonates as potent inhibitors of 15-lipoxygenase from soybeans.
A number of indolizine 1-sulfonates have been prepared by cyclization of cyclopropenones with pyridines followed by trapping of the intermediate 1-indolizinol with a sulfonyl halide, and examined as inhibitors of 15-lipoxygenase (15-LO). The compounds display IC(50) values between 15 and 42 microM; all are more active than the well-known 15-LO inhibitor quercetin (IC(50) 51 microM). A wide variety of substituents are well tolerated. The enzyme inhibition was not affected by preincubation or the presence of a detergent and no significant particle formation was observed. Hence, inhibition from aggregates of indolizines, promiscuous inhibition, is highly unlikely.
Teklu
Solomon
S
Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway.
Gundersen
Lise-Lotte
LL
Larsen
Tove
T
Malterud
Karl E
KE
Rise
Frode
F
D001190:Arylsulfonates / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007212:Indolizines / Q000138:chemical synthesis / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D013025:Glycine max / Q000201:enzymology*
D001190:Arylsulfonates; D004791:Enzyme Inhibitors; D007212:Indolizines; D016859:Lipoxygenase Inhibitors