Hall I H, Burnham B S, Rajendran K G, Chen S Y, Sood A, Spielvogel B F, Shaw B R
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Biomed Pharmacother. 1993;47(2-3):79-87. doi: 10.1016/0753-3322(93)90295-v.
Base-boronated nucleoside and phosphate-boronated nucleotides were potent hypolipidemic agents in rodents, lowering both serum cholesterol and triglyceride levels. Rat VLDL and LDL cholesterol levels were generally reduced and HDL cholesterol levels were significantly elevated after 14 days dosing at 8 mg/kg/day. Tissue cholesterol, triglyceride and phospholipid levels were reduced by selected derivatives. Increased fecal excretion of lipids did not appear to be a mechanism by which these derivatives lowered serum lipids in rodents. Rather, the agents suppressed appetite and reduced the activities of rate-limiting enzymes for de novo lipid synthesis, specifically cytoplasmic acetyl CoA synthetase, squalene synthetase, and phosphatidylate phosphohydrolase with IC50 values of approximately 10(-5) m.
碱基硼化核苷和磷酸硼化核苷酸是啮齿动物中有效的降血脂剂，可降低血清胆固醇和甘油三酯水平。在以8mg/kg/天的剂量给药14天后，大鼠极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）胆固醇水平通常降低，高密度脂蛋白（HDL）胆固醇水平显著升高。特定衍生物可降低组织中的胆固醇、甘油三酯和磷脂水平。脂质粪便排泄增加似乎不是这些衍生物降低啮齿动物血清脂质的机制。相反，这些药剂抑制食欲，并降低从头合成脂质的限速酶的活性，特别是细胞质乙酰辅酶A合成酶、角鲨烯合成酶和磷脂酸磷酸水解酶，其半数抑制浓度（IC50）值约为10^(-5) m。
