Marine bis-γ-pyrone polypropionates of onchidione family and their effects on the XBP1 gene expression

Bioorg Med Chem Lett. 2018 Apr 1;28(6):1093-1096. doi: 10.1016/j.bmcl.2018.02.010. Epub 2018 Feb 8.

Abstract

Two additional new members of the onchidione family, 16-epi-onchidione (1) and 4-epi-onchidione (2), co-occurring with six previously reported bis-γ-pyrone polypropionates including onchidione (3), were isolated from the marine pulmonate Onchidium sp. Their structures were determined by extensive spectroscopic analysis and by comparison with 3 and onchidione-related derivatives. The absolute configuration of 1 was established by X-ray diffraction analysis employing graphite monochromated Cu Kα radiation (λ = 0.71073 Å) with small Flack parameter 0.08. In addition, the absolute stereochemistry of previously reported onchidionol (6) was confirmed by the X-ray diffraction analysis. Some of the isolated compounds showed significant activation effects on the splicing of XBP1 mRNA as ER stress modulators to inhibit the growth of tumors.

Keywords: Absolute configuration; Polypropionates; Pulmonate; XBP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Gastropoda / chemistry
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pyrones / chemical synthesis
  • Pyrones / chemistry
  • Pyrones / pharmacology*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • Structure-Activity Relationship
  • X-Box Binding Protein 1 / antagonists & inhibitors*
  • X-Box Binding Protein 1 / genetics

Substances

  • Pyrones
  • RNA, Messenger
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • onchidione