A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase (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.

Aminopropylindenes derived from Grundmann’s ketone as a novel chemotype of oxidosqualene cyclase inhibitors.

OLIARO BOSSO, Simonetta;BALLIANO, Gianni;
2013

Abstract

A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase (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.
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S. Lange; M. Keller; C. Müller; S. Oliaro-Bosso;G. Balliano; F. Bracher
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/132660
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