Allylphenols as a new class of human 15-lipoxygenase-1 inhibitors

Drug Dev Res. 2021 Apr;82(2):259-266. doi: 10.1002/ddr.21749. Epub 2020 Oct 6.

Abstract

In this study, a series of mono- and diallylphenol derivative were designed, synthesized, and evaluated as potential human 15-lipoxygenase-1 (15-hLOX-1) inhibitors. Radical scavenging potency of the synthetic allylphenol derivatives was assessed and the results were in accordance with lipoxygenase (LOX) inhibition potency. It was found that the electronic natures of allyl moiety and para substituents play the main role in radical scavenging activity and subsequently LOX inhibition potency of the synthetic inhibitors. Among the synthetic compounds, 2,6-diallyl-4-(hexyloxy)phenol (42) and 2,6-diallyl-4-aminophenol (47) showed the best results for LOX inhibition (IC50 = 0.88 and 0.80 μM, respectively).

Keywords: 15-hLOX-1; Claisen rearrangement; DPPH; MBTH; allylphenol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 15-Lipoxygenase / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / pharmacology*
  • Phenols / chemistry*
  • Phenols / pharmacology*

Substances

  • Lipoxygenase Inhibitors
  • Phenols
  • ALOX15 protein, human
  • Arachidonate 15-Lipoxygenase