2,3-oxidosqualene cyclase: From azasqualenes to new site-directed inhibitors

摘要: 2,3-Oxidosqualene cyclases (OSC) are enzymes which convert 2,3-oxidosqualene (OS) into polycyclic triterpenoids such as lanosterol, cycloartenol, and α-and β-amyrin. Our interest in the study of OSC is development new inhibitors for potential use hypocholesterolemic, antifungal, or phytotoxic drugs. In particular, we describe biological activity mechanism a series acyclic azasqualene derivatives mimicking C-2, C-8, C-20 carbonium ions formed during OS cyclization. Some these ion analogues very promising specific hypocholesterolemic agents. The toxicity, biodistribution, pharmacokinetics different mice also presented. order to obtain new, site-directed irreversible OSC, squalene containing functional groups that can link covalently an active-site thiol group was designed. Among compounds, maleimide most active toward mammalian whereas Ellman behaved inhibitor from yeast