Novel squalene-hopene cyclase inhibitors derived from hydroxycoumarins and hydroxyacetophenones.
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.
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino, Italy. giancarlo.cravotto@unito.it
Giancarlo
G
Cravotto
Gianni
G
Balliano
Silvia
S
Tagliapietra
Simonetta
S
Oliaro-Bosso
Gian Mario
GM
Nano
D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry*; D001406:Bacillaceae / Q000737:chemistry; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000138:chemical synthesis / Q000737:chemistry*
D000098:Acetophenones; D014468:Umbelliferones; C019339:2,6-dihydroxyacetophenone; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase