Marine natural products as inhibitors of cystathionine beta-synthase activity

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1064-6. doi: 10.1016/j.bmcl.2015.01.013. Epub 2015 Jan 14.

Abstract

A library consisting of characterized marine natural products as well as synthetic derivatives was screened for compounds capable of inhibiting the production of hydrogen sulfide (H2S) by cystathionine beta-synthase (CBS). Eight hits were validated and shown to inhibit CBS activity with IC50 values ranging from 83 to 187μM. The majority of hits came from a series of synthetic polyandrocarpamine derivatives. In addition, a modified fluorogenic probe for H2S detection with improved solubility in aqueous solutions is reported.

Keywords: Fluorogenic probe; Hydrogen sulfide; Inhibitor screen; Sulfur metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Amines / isolation & purification
  • Amines / pharmacology
  • Animals
  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology
  • Cystathionine beta-Synthase / antagonists & inhibitors*
  • Cystathionine beta-Synthase / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrogen Sulfide / analysis
  • Hydrogen Sulfide / metabolism*
  • Imidazoles / chemistry*
  • Imidazoles / isolation & purification
  • Imidazoles / pharmacology
  • Urochordata / chemistry*

Substances

  • Amines
  • Biological Products
  • Enzyme Inhibitors
  • Imidazoles
  • polyandrocarpamine A
  • polyandrocarpamine B
  • Cystathionine beta-Synthase
  • Hydrogen Sulfide