1. Academic Validation
  2. Inhibition of neutral lipid synthesis by avarols from a marine sponge

Inhibition of neutral lipid synthesis by avarols from a marine sponge

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2283-2285. doi: 10.1016/j.bmcl.2019.06.026.
Taichi Ohshiro 1 Keisuke Kobayashi 2 Aika Suzuki 3 Hiroyuki Yamazaki 4 Ryuji Uchida 4 Michio Namikoshi 4 Hiroshi Tomoda 5
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Tokyo, Japan. Electronic address: ohshirot@pharm.kitasato-u.ac.jp.
  • 2 Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Tokyo, Japan.
  • 3 Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan.
  • 4 Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
  • 5 Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Tokyo, Japan. Electronic address: tomodah@pharm.kitasato-u.ac.jp.
Abstract

The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in CHO-K1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (CE) and triglyceride (TG) with IC50 values of 5.74 and 6.80 µM, respectively. In Enzyme assays, sterol O-acyltransferase (SOAT), the final Enzyme involved in CE biosynthesis, and diacylglycerol Acyltransferase (DGAT), the final Enzyme involved in TG biosynthesis, were inhibited by 1 with IC50 values of 7.31 and 20.0 µM, respectively, which correlated well with those obtained in the intact cell assay. These results strongly suggest that 1 inhibited SOAT and DGAT activities in CHO-K1 cells, leading to a reduction in the accumulation of CE and TG in lipid droplets.

Keywords

Inhibitor; Neutral lipid synthesis; Sesquiterpene hydroquinone.

Figures