Synthesis and biological activity of 19-azasqualene 2,3-epoxide as inhibitor of 2,3-oxidosqualene cyclase

M. Ceruti, F. Rocco, F. Viola, G. Balliano, G. Grosa, F. Dosio, L. Cattel

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

19-Azasqualene 2,3-epoxide and its N-oxide, high-energy intermediate analogue inhibitors of 2,3-oxidosqualene (SO) cyclase, were obtained by total synthesis. These compounds were designed to mimic the C-20 carbonium ion precursor of lanosterol formed during SO cyclization. The synthesis involved the preparation of C22 squalenoid aldehyde epoxide through a new procedure and the reconstruction of the squalenoid chain bearing a nitrogen at C-19 (pro C-20). 19-Azasqualene 2,3-epoxide was active on SO cyclase from rat and pig liver with an IC50 of 1.5 μM in pig, while in SO cyclases of yeast (S cerevisiae and C albicans) microsomes it was 20-30-fold less active. It was inactive on squalene epoxidase from rat and pig liver at the highest concentrations tested (100 μM).

Lingua originaleInglese
pagine (da-a)675-682
Numero di pagine8
RivistaEuropean Journal of Medicinal Chemistry
Volume28
Numero di pubblicazione9
DOI
Stato di pubblicazionePubblicato - 1993
Pubblicato esternamente

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