Chemical & Pharmaceutical Bulletin 2004-10-01

Novel squalene-hopene cyclase inhibitors derived from hydroxycoumarins and hydroxyacetophenones.

Giancarlo Cravotto, Gianni Balliano, Silvia Tagliapietra, Simonetta Oliaro-Bosso, Gian Mario Nano

Index: Chem. Pharm. Bull. 52(10) , 1171-4, (2004)

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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 omega-epoxyfarnesyl moiety or just a plain alkyl chain showed an inhibitory effect on a recombinant SHC from Alicyclobacillus acidocaldarius expressed in Escherichia coli.