HYPOLIPIDEMIC ACTIVITY OF BORONATED NUCLEOSIDES AND NUCLEOTIDES IN RODENTS
HYPOLIPIDEMIC ACTIVITY OF BORONATED NUCLEOSIDES AND NUCLEOTIDES IN RODENTS
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DOI：
10.1016/0753-3322(93)90295-v
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发表时间：
1993-01-01
影响因子：
7.5
通讯作者：
SHAW, BR
中科院分区：
文献类型：
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作者：
HALL, IH;BURNHAM, BS;SHAW, BR
碱式硼化核苷和磷酸-硼化核苷酸对啮齿类动物都是有效的降血脂药物，可以降低血清胆固醇和甘油三酯水平。给药14天后，大鼠极低密度脂蛋白和低密度脂蛋白水平普遍降低，高密度脂蛋白水平显著升高。组织胆固醇、甘油三酯和磷脂水平通过选择的衍生物降低。增加粪便中脂质的排泄似乎不是这些衍生物降低啮齿动物血脂的机制。相反，这些药物抑制食欲，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酰磷酸水解酶，其IC50值约为10(-5)m。
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.