Chemical modification and structure-activity relationships of pyripyropenes .1. Modification at the four hydroxyl groups
Chemical modification and structure-activity relationships of pyripyropenes .1. Modification at the four hydroxyl groups
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DOI：
10.7164/antibiotics.49.1133
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发表时间：
1996-11-01
影响因子：
3.3
通讯作者：
Omura, S
中科院分区：
文献类型：
--
作者：
Obata, R;Sunazuka, T;Omura, S
四个羟基的啶南平已被修改和评价其能力，以抑制微粒体酰基辅酶A：胆固醇酰基转移酶（ACAT）的活性在体外和降低胆固醇吸收在体内的胆固醇喂养仓鼠。7-O-n-戊酰基衍生物（8 c）改善体外ACAT抑制活性（IC 50 =13 nM），比啶南平A好约7倍。在11-羟基（17 a）处引入甲磺酰基增加了体外活性（IC 50 =19 nM）和体内功效（艾德（50）=10 mg/kg）。
Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50=13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity (IC50=19 nM) and in vivo efficacy (ED(50)=10 mg/kg).