Easy and rapid preparation of benzoylhydrazides and their diazene derivatives as inhibitors of 15-lipoxygenase

Bioorg Med Chem Lett. 2017 Apr 15;27(8):1649-1653. doi: 10.1016/j.bmcl.2017.03.017. Epub 2017 Mar 8.

Abstract

Two series of diaza derivatives were prepared by solvent-free condensation of benzoic acid and 4-substituted phenylhydrazines in order to obtain phenylhydrazides (HYD series) and, by oxidation of these compounds, the corresponding benzoyldiazenes (DIA series). Both sets were evaluated as inhibitors of soybean 15-lipoxygenase activity and antioxidant capability in the FRAP and CUPRAC assays. The most potent inhibitors of both series exhibited IC50 values in the low micromolar range. Kinetic studies showed that at least the more active compounds were competitive inhibitors. Docking results indicated that the most potent inhibitor interacts strongly with Ile-839 and iron in the active site.

Keywords: 15-Lipoxygenase inhibition; Antioxidant capability; Benzoyldiazene; Lipophilicity; Phenylhydrazides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Benzoates / chemical synthesis
  • Benzoates / chemistry*
  • Benzoates / pharmacology
  • Chemistry Techniques, Synthetic / economics
  • Chemistry Techniques, Synthetic / methods
  • Glycine max / drug effects
  • Glycine max / enzymology
  • Humans
  • Hydrazines / chemical synthesis
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology
  • Imides / chemical synthesis
  • Imides / chemistry*
  • Imides / pharmacology
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / pharmacology
  • Molecular Docking Simulation
  • Oxidation-Reduction
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Benzoates
  • Hydrazines
  • Imides
  • Lipoxygenase Inhibitors
  • Arachidonate 15-Lipoxygenase
  • diazene