|
化学名
|
[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate
|
分子式
|
C25H38O5
|
|
详细内容
|
Simvastatin (SIM), a lactone, is white, crystalline, nonhygroscopic and powdery, practically insoluble in water (30 mcg/ml), and 0.1 (N) HCl (60 mcg/ml). Its precursor is a fermentation product of Aspergillus terreus. It is used for treating coronary heart disease, hyperlipidemia, hypercholesterolemia, atherosclerosis and stroke [1] [2]. SIM is biologically inactive. Oral ingestion hydrolyzed it into the β-hydroxyacid form which is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase [2]. In human lung microvascular endothelial cells, it increased the amount of endothelial nitric oxide synthase mRNA [3]. Simvastatin had anti-cancer properties [1]. Its IC50 to inhibit P-glycoprotein is 9 μM [4].
HMG CoA reductase catalyses an early rate-limiting step in the biosynthesis of cholesterol [2].
In both cell lines HepG2 and Huh7, both doses of simvastatin (32 and 64 μM) had a significant inhibitory effect on tumor cell growth as compared to controls (p<0.05). This effect was time-dependent, a simvastatin pre-treatment for 48 h or 72 h significantly reduced cell growth as compared to 24 h pre-incubation (p<0.05). Simvastatin treatment for 48 or 72 h made HepG2 cells exhibit downregulation of CDK1, CDK2, CDK4 and cyclins D1 and E as compared to control tumor cells. Simvastatin treatment for 24, 48 and 72 h made relative expression of cyclin-dependent kinase inhibitors p19 and p27 enhance as compared to control tumor cells [1].
In patients with polygenic hypercholesterolemia and allocated to diet plus 20 mg/day simvastatin for 8 weeks, total cholesterol (-27%), low density lipoproteincholesterol (-33%), and monocyte expression of TNF (-49%) and IL-1( (-35%) significantly decreased (p<0.02) [5].
|