Design and Synthesis of Structure-Simplified Derivatives of Gonytolide for the Promotion of Innate Immune Responses

J Nat Prod. 2016 May 27;79(5):1259-66. doi: 10.1021/acs.jnatprod.5b00829. Epub 2016 Apr 15.

Abstract

Gonytolide A (1), a dimeric chromanone substituted with the γ-lactone, shows promoting activity of innate immune responses. However, biological studies on this compound have been limited by the low amounts of 1 available from natural resources and the difficulty of its synthesis. In this study, we designed and synthesized structure-simplified gonytolide derivatives. Bischromone 10 and biflavone 13 both promoted the mammalian TNF-α signaling pathway and Drosophila innate immunity. They did not contain a chiral center and were easy to synthesize. Hence, they can be used as lead compounds for a new type of immunostimulating drugs and as research reagents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromones* / chemical synthesis
  • Chromones* / chemistry
  • Chromones* / pharmacology
  • Drosophila / metabolism*
  • Drug Design
  • Immunity, Innate / drug effects*
  • Lactones* / chemical synthesis
  • Lactones* / chemistry
  • Lactones* / pharmacology
  • Molecular Structure
  • Signal Transduction
  • Stereoisomerism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chromones
  • Lactones
  • Tumor Necrosis Factor-alpha
  • gonytolide A