{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:35:50Z","timestamp":1761006950136,"version":"build-2065373602"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[1992,3,1]],"date-time":"1992-03-01T00:00:00Z","timestamp":699408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lipids"],"published-print":{"date-parts":[[1992,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Two squalene derivatives, trisnorsqualene cyclopropylamine and trisnorsqualene<jats:italic>N<\/jats:italic>\u2010methylcyclopropylamine, were synthesized and tested for inhibition of lanosterol and squalene epoxide formation from squalene in rat hepatic microsomes, and for the inhibition of cholesterol syntheses in human cultured hepatoblastoma (HepG2) cells. Trisnorsqualene cyclopropylamine inhibited [<jats:sup>3<\/jats:sup>H]\u2010squalene conversion to [<jats:sup>3<\/jats:sup>H]squalene epoxide in microsomes (IC<jats:sub>50<\/jats:sub>=5.0 \u03bcM), indicating that this derivative inhibited squalene mono\u2010oxygenase. Trisnorsqualene<jats:italic>n<\/jats:italic>\u2010methylcyclopropylamine inhibited [<jats:sup>3<\/jats:sup>H]squalene conversion to [<jats:sup>3<\/jats:sup>H]lanosterol (IC<jats:sub>50<\/jats:sub>=12.0 \u03bcM) and caused [<jats:sup>3<\/jats:sup>H]\u2010squalene epoxide to accumulate in microsomes, indicating that this derivative inhibited 2,3\u2010oxidosqualene cyclase. Cholesterol biosynthesis from [<jats:sup>14<\/jats:sup>C]acetate in HepG2 cells was inhibited by both derivatives (IC<jats:sub>50<\/jats:sub>=1.0 \u03bcM for trisnorsqualene cyclopropylamine; IC<jats:sub>50<\/jats:sub>=0.5 \u03bcM for trisnorsqualene<jats:italic>N<\/jats:italic>\u2010methylcyclopropylamine). Cells incubated with trisnorsqualene cyclopropylamine accumulated [<jats:sup>14<\/jats:sup>C]squalene, while cells incubated with trisnorsqualene<jats:italic>N<\/jats:italic>\u2010methylcyclopropylamine accumulated [<jats:sup>14<\/jats:sup>C]squalene epoxide and [<jats:sup>14<\/jats:sup>C]squalene diepoxide. The concentration range of inhibitor which caused these intermediates to accumulate coincided with that which inhibited cholesterol synthesis. The results indicate that cyclopropylamine derivatives of squalene are effective inhibitors of cholesterol synthesis, and that substitutions at the nitrogen affect enzyme selectivity and thus the mechanism of action of the compounds.<\/jats:p>","DOI":"10.1007\/bf02536171","type":"journal-article","created":{"date-parts":[[2006,11,29]],"date-time":"2006-11-29T08:29:18Z","timestamp":1164788958000},"page":"157-160","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of cholesterol synthesis by cyclopropylamine derivatives of squalene in human hepatoblastoma cells in culture"],"prefix":"10.1002","volume":"27","author":[{"given":"W. A.","family":"Van Sickle","sequence":"first","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. Cincinnati OH 45215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. R.","family":"Angelastro","sequence":"additional","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. Cincinnati OH 45215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. Cincinnati OH 45215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. R.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. Cincinnati OH 45215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Marquart","sequence":"additional","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. Cincinnati OH 45215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Marion Merrell Dow Research Institute 2110 E. Galbraith Rd. 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