Aminopropylindenes derived from Grundmann's ketone as a novel chemotype of oxidosqualene cyclase inhibitors.
A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann's ketone. Screening on OSCs from five different organisms revealed interesting activities and selectivities of some of the compounds. A N,N-dimethylaminopropyl derivative showed promising inhibition of Trypanosoma cruzi OSC in combination with low cytotoxicity, and showed significant reduction of cholesterol biosynthesis in a human cell line.
T10 T11 T12 T13 T14 T1 T2 T3 T4 T5 T6 T7 T8 T9
GENE-Y GENE-N GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
OSC OSCs Trypanosoma cruzi OSC oxidosqualene cyclase(1) oxidosqualene cyclase aminopropylindenes 2,3-oxidosqualen lanosterol Grundmann's ketone N,N-dimethylaminopropyl cholesterol oxidosqualene Aminopropylindenes Grundmann's ketone