Ohshiro Taichi, Matsuda Daisuke, Nagai Kenichiro, Doi Takayuki, Sunazuka Toshiaki, Takahashi Takashi, Rudel Lawrence Lee, Omura Satoshi, Tomoda Hiroshi
Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 2009 Apr;57(4):377-81. doi: 10.1248/cpb.57.377.
The selectivity of synthetic beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA : cholesterol acyltrasferase (ACAT), ACAT1 and ACAT2, was studied in cell-based assays using ACAT1- or ACAT2-expressing Chinese hamster ovary (CHO) cells. NBV274, 285 and 300 showed ACAT1 selective inhibition similar to that of natural beauveriolides I and III, NBV345 inhibited both isozymes with similar potency, but NBV281, 331 and 249 were found to selectively inhibit the ACAT2 isozyme. The structure-activity relationships indicated that a subtle structural difference in beauveriolide derivatives can affect the selectivity of inhibition of the ACAT isozymes.
利用表达ACAT1或ACAT2的中国仓鼠卵巢（CHO）细胞，在基于细胞的分析中研究了合成白僵菌素衍生物对酰基辅酶A：胆固醇酰基转移酶（ACAT）的两种同工酶ACAT1和ACAT2的抑制选择性。NBV274、285和300表现出与天然白僵菌素I和III相似的ACAT1选择性抑制作用，NBV345对两种同工酶的抑制效力相似，但发现NBV281、331和249选择性抑制ACAT2同工酶。构效关系表明，白僵菌素衍生物中细微的结构差异会影响对ACAT同工酶抑制的选择性。
