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 IC50 values between 15 and 42 μM; all are more active than the well-known 15-LO inhibitor quercetin (IC50 51 μM). 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.

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