Microcystins: Synthesis and structure-activity relationship studies toward PP1 and PP2A

Bioorg Med Chem. 2018 Mar 15;26(6):1118-1126. doi: 10.1016/j.bmc.2017.08.040. Epub 2017 Aug 24.

Abstract

Microcystins are highly toxic cyanotoxins responsible for plant, animal and human poisoning. Exposure to microcystins, mainly through drinkable water and contaminated food, is a current world health concern. Although it is quite challenging, the synthesis of these potent cyanotoxins, analogs and derivatives helps to evaluate their toxicological properties and to elucidate their binding mechanisms to their main targets Protein Phosphatase-1 (PP1) and -2A (PP2A). This review focuses on synthetic approaches to prepare microcystins and analogs and compiles structure-activity relationship (SAR) studies that describe the unique features of microcystins that make them so potent.

Keywords: Inhibitors; Medicinal chemistry; Microcystin; Protein phosphatases; Structure-activity relationship.

Publication types

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

MeSH terms

  • Binding Sites
  • Humans
  • Microcystins / chemical synthesis
  • Microcystins / chemistry*
  • Microcystins / metabolism
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Phosphatase 1 / chemistry
  • Protein Phosphatase 1 / metabolism*
  • Protein Phosphatase 2 / chemistry
  • Protein Phosphatase 2 / metabolism*
  • Structure-Activity Relationship

Substances

  • Microcystins
  • Protein Phosphatase 1
  • Protein Phosphatase 2