当前位置：
X-MOL 学术
›
Bioorg. Med. Chem. Lett.
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Inhibition of cholesteryl ester synthesis by polyacetylenes from Atractylodes rhizome.
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.bmcl.2020.126997 Elyza Aiman Azizah Nur 1 , Taichi Ohshiro 2 , Keisuke Kobayashi 2 , Jing Wu 3 , Elly Wahyudin 4 , Huiping Zhang 5 , Fumiaki Hayashi 5 , Hirokazu Kawagishi 3 , Hiroshi Tomoda 2
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.bmcl.2020.126997 Elyza Aiman Azizah Nur 1 , Taichi Ohshiro 2 , Keisuke Kobayashi 2 , Jing Wu 3 , Elly Wahyudin 4 , Huiping Zhang 5 , Fumiaki Hayashi 5 , Hirokazu Kawagishi 3 , Hiroshi Tomoda 2
Affiliation
|
Using activity guided purification, four known compounds, sesquiterpene atractylenolide III (1), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol (2), 14-acetoxy-12-α-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (3), and 14-acetoxy-12-β -methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (4), were isolated from a traditional herbal medicine, Atractylodes rhizome. Structurally similar 3 and 4 (3/4 mixture) were obtained as a mixture. In intact Chinese hamster ovary (CHO) K1 cell assays, 1, 2, and a 3/4 mixture selectively inhibited cholesterol [14C]oleate synthesis from [14C]oleate with IC50 values of 73.5 µM, 35.4 µM, and 10.2 µM, respectively, without any effects on cytotoxicity. As a potential target of these inhibitors involved in cholesteryl ester (CE) synthesis, effects on sterol O-acyltransferase (SOAT) activity were investigated using microsomes prepared from CHO-K1 cells as an enzyme source. Hence, these compounds inhibit SOAT activity with IC50 values (211 µM for 1, 29.0 µM for 2, and 11.8 µM for 3/4 mixture) that correlate well with those measured from intact cell assays. Our results strongly suggest that these compounds inhibit CE synthesis by blocking SOAT activity in CHO-K1 cells.
更新日期：2020-01-26
京公网安备 11010802027423号