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

doi:10.1016/0223-5234(93)90026-B

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

Research output: Contribution to journal › Article › peer-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).

Original language	English
Pages (from-to)	675-682
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	28
Issue number	9
DOIs	https://doi.org/10.1016/0223-5234(93)90026-B
Publication status	Published - 1993
Externally published	Yes

Keywords

2,3-oxidosqualene cyclase inhibitors
antifungals
epoxy azasqualenes
hypocholesterolemics

Access to Document

10.1016/0223-5234(93)90026-B

Cite this

@article{8274503c59cf4abdac678b053da1ecb2,

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

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).",

keywords = "2,3-oxidosqualene cyclase inhibitors, antifungals, epoxy azasqualenes, hypocholesterolemics",

author = "M. Ceruti and F. Rocco and F. Viola and G. Balliano and G. Grosa and F. Dosio and L. Cattel",

year = "1993",

doi = "10.1016/0223-5234(93)90026-B",

language = "English",

volume = "28",

pages = "675--682",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

number = "9",

}

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 - https://www.scopus.com/pages/publications/0027428937

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 -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this