Obata R, Sunazuka T, Li Z, Tian Z, Harigaya Y, Tabata N, Tomoda H, Omura S
Research Center for Biological Function, Kitasato Institute, Kitasato University, Tokyo, Japan.
J Antibiot (Tokyo). 1996 Nov;49(11):1133-48. doi: 10.7164/antibiotics.49.1133.
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 (ED50 = 10 mg/kg).
对双吡咯并吡咯类化合物的四个羟基进行了修饰，并评估了它们在体外抑制微粒体酰基辅酶A：胆固醇酰基转移酶（ACAT）活性以及在体内降低胆固醇喂养仓鼠胆固醇吸收的能力。7-O-正戊酰基衍生物（8c）的体外ACAT抑制活性（IC50 = 13 nM）比双吡咯并吡咯A提高了约7倍。在11-羟基处引入甲磺酰基（17a）提高了体外活性（IC50 = 19 nM）和体内疗效（ED50 = 10 mg/kg）。
