TY - JOUR
T1 - Synthesis and biological activity of 19-azasqualene 2,3-epoxide as inhibitor of 2,3-oxidosqualene cyclase
AU - Ceruti, M.
AU - Rocco, F.
AU - Viola, F.
AU - Balliano, G.
AU - Grosa, G.
AU - Dosio, F.
AU - Cattel, L.
PY - 1993
Y1 - 1993
N2 - 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).
AB - 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).
KW - 2,3-oxidosqualene cyclase inhibitors
KW - antifungals
KW - epoxy azasqualenes
KW - hypocholesterolemics
UR - http://www.scopus.com/inward/record.url?scp=0027428937&partnerID=8YFLogxK
U2 - 10.1016/0223-5234(93)90026-B
DO - 10.1016/0223-5234(93)90026-B
M3 - Article
SN - 0223-5234
VL - 28
SP - 675
EP - 682
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 9
ER -