Insights into the myosin II inhibitory potency of A-ring-modified (S)-blebbistatin analogs

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2986-2989. doi: 10.1016/j.bmcl.2017.05.008. Epub 2017 May 4.

Abstract

Myosin II is an interesting target for therapeutic intervention, as it is involved in a large number of motility-based diseases. (S)-Blebbistatin is a known micromolar inhibitor of this protein. A new series of (S)-blebbistatin derivatives with a modified A-ring was synthesized and the myosin II inhibitory properties were evaluated in vitro. In this way, we gained insight into the influence of structural modifications in this part of the scaffold on myosin II inhibitory potency. Our results indicate there are few possibilities for potency enhancement via ring A modification of the blebbistatin scaffold.

Keywords: A-ring modification; Blebbistatin; Myosin II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dictyostelium / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Molecular Structure
  • Myosin Type II / antagonists & inhibitors*
  • Myosin Type II / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Myosin Type II