TY - JOUR
T1 - Synthesis of a squalenoid oxaziridine and other new classes of squalene derivatives, as inhibitors of sterol biosynthesis
AU - Ceruti, Maurizio
AU - Viola, Franca
AU - Balliano, Gianni
AU - Grosa, Giorgio
AU - Caputo, Otto
AU - Gerst, Nicolas
AU - Schuber, Francis
AU - Cattel, Luigi
PY - 1988
Y1 - 1988
N2 - New classes of squalene derivatives, rationally designed as inhibitors of 2,3-oxidosqualene (SO) cyclase, a key enzyme in sterol biosynthesis, were synthesized. These were: N-methylimine 7, aminalic hydroperoxide 8, N-methyloxaziridine 9 and N-methylamide 10.9 was synthesized by a new method, in order to prevent acid decomposition of 7 and 9. The inhibitory activities of 7-10 were determined in vitro on SO cyclase associated with rat liver and yeast microsomes, and in vivo on sterol biosynthesis in 3T3 fibroblast cultures. 9 was the best inhibitor of SO cyclase associated with rat liver and yeast microsomes. In contrast, 7 and 10 strongly inhibited biosynthesis of C27-sterols in 3T3 fibroblast cultures.
AB - New classes of squalene derivatives, rationally designed as inhibitors of 2,3-oxidosqualene (SO) cyclase, a key enzyme in sterol biosynthesis, were synthesized. These were: N-methylimine 7, aminalic hydroperoxide 8, N-methyloxaziridine 9 and N-methylamide 10.9 was synthesized by a new method, in order to prevent acid decomposition of 7 and 9. The inhibitory activities of 7-10 were determined in vitro on SO cyclase associated with rat liver and yeast microsomes, and in vivo on sterol biosynthesis in 3T3 fibroblast cultures. 9 was the best inhibitor of SO cyclase associated with rat liver and yeast microsomes. In contrast, 7 and 10 strongly inhibited biosynthesis of C27-sterols in 3T3 fibroblast cultures.
KW - 2,3-oxidosqualene cyclase inhibitors
KW - 3T3 fibroblasts
KW - polyenic oxaziridines
KW - rat liver and yeast microsomes
KW - squalene derivatives
UR - http://www.scopus.com/inward/record.url?scp=0024272462&partnerID=8YFLogxK
U2 - 10.1016/0223-5234(88)90096-7
DO - 10.1016/0223-5234(88)90096-7
M3 - Article
SN - 0223-5234
VL - 23
SP - 533
EP - 537
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 6
ER -