Inhibition of neutral lipid synthesis by avarols from a marine sponge

Taichi Ohshiro; Keisuke Kobayashi; Aika Suzuki; Hiroyuki Yamazaki; Ryuji Uchida; Michio Namikoshi; Hiroshi Tomoda

doi:10.1016/j.bmcl.2019.06.026

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. Epub 2019 Jun 19.

Authors

Taichi Ohshiro¹, Keisuke Kobayashi², Aika Suzuki³, Hiroyuki Yamazaki⁴, Ryuji Uchida⁴, Michio Namikoshi⁴, Hiroshi Tomoda⁵

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.

PMID: 31253530
DOI: 10.1016/j.bmcl.2019.06.026

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CHO Cells
Cricetulus
Dose-Response Relationship, Drug
Lipid Droplets / drug effects
Lipids / antagonists & inhibitors*
Lipids / chemical synthesis
Lipids / chemistry
Molecular Structure
Particle Size
Porifera
Sesquiterpenes / chemical synthesis
Sesquiterpenes / chemistry
Sesquiterpenes / pharmacology*
Structure-Activity Relationship
Surface Properties

Substances

Lipids
Sesquiterpenes
avarol