Novel Squalene-Hopene Cyclase Inhibitors Derived from Hydroxycoumarins and Hydroxyacetophenones

Abstract

Squalene-hopene cyclase (SHC) is a useful model enzyme for predicting molecular interactions with oxidosqualene cyclase (OSC). Structure–activity relationships were investigated for numerous coumarin-derived inhibitors of SHC, and structural simplifications are suggested. Both umbelliferone and 2,4-dihydroxyacetophenone provide convenient starting nuclei for the design of SHC inhibitors. Derivatives bearing an ω-epoxyfarnesyl moiety or just a plain alkyl chain showed an inhibitory effect on a recombinant SHC from Alicyclobacillus acidocaldarius expressed in Escherichia coli.