Publication Date:
2020
Description:
〈p〉Publication date: Available online 25 January 2020〈/p〉
〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉
〈p〉Author(s): Elyza Aiman Azizah Nur, Taichi Ohshiro, Keisuke Kobayashi, Jing Wu, Elly Wahyudin, Huiping Zhang, Fumiaki Hayashi, Hirokazu Kawagishi, Hiroshi Tomoda〈/p〉
〈div xml:lang="en"〉
〈h5〉Abstract〈/h5〉
〈div〉〈p〉Using activity guided purification, four known compounds, sesquiterpene atractylenolide III (〈strong〉1〈/strong〉), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2〈em〉E〈/em〉,8〈em〉E〈/em〉,10〈em〉E〈/em〉-trien-4,6-diyn-1-ol (〈strong〉2〈/strong〉), 14-acetoxy-12-α-methylbutyl-2〈em〉E〈/em〉,8〈em〉E〈/em〉,10〈em〉E〈/em〉-trien-4,6-diyn-1-ol (〈strong〉3〈/strong〉), and 14-acetoxy-12-β -methylbutyl-2〈em〉E〈/em〉,8〈em〉E〈/em〉,10〈em〉E〈/em〉-trien-4,6-diyn-1-ol (〈strong〉4〈/strong〉), were isolated from a traditional herbal medicine, 〈em〉Atractylodes〈/em〉 rhizome. Structurally similar 〈strong〉3〈/strong〉 and 〈strong〉4〈/strong〉 (〈strong〉3〈/strong〉/〈strong〉4〈/strong〉 mixture) were obtained as a mixture. In intact Chinese hamster ovary (CHO) K1 cell assays, 〈strong〉1〈/strong〉, 〈strong〉2〈/strong〉, and a 〈strong〉3〈/strong〉/〈strong〉4〈/strong〉 mixture selectively inhibited cholesterol [〈sup〉14〈/sup〉C]oleate synthesis from [〈sup〉14〈/sup〉C]oleate with IC〈sub〉50〈/sub〉 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 〈em〉O〈/em〉-acyltransferase (SOAT) activity were investigated using microsomes prepared from CHO-K1 cells as an enzyme source. Hence, these compounds inhibit SOAT activity with IC〈sub〉50〈/sub〉 values (211 µM for 〈strong〉1〈/strong〉, 29.0 µM for 〈strong〉2〈/strong〉, and 11.8 µM for 〈strong〉3〈/strong〉/〈strong〉4〈/strong〉 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.〈/p〉〈/div〉
〈/div〉
〈div xml:lang="en"〉
〈h5〉Graphical abstract〈/h5〉
〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X20300603-ga1.jpg" width="334" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉
〈/div〉
Print ISSN:
0960-894X
Electronic ISSN:
1464-3405
Topics:
Chemistry and Pharmacology
,
Medicine
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