2-(2-Methylfuran-3-carboxamido)-3-phenylpropanoic acid, a potential CYP26A1 inhibitor to enhance all-trans retinoic acid-induced leukemia cell differentiation based on virtual screening and biological evaluation

Bioorg Med Chem. 2013 Jun 1;21(11):3256-61. doi: 10.1016/j.bmc.2013.03.044. Epub 2013 Apr 3.

Abstract

To develop new CYP26A1 inhibitors, a three-cycle virtual screening was carried out based on the constructed homology model of human CYP26A1 using Dock, Fred, Gold and AutoDock. Twenty-two compounds exhibited high scores and reasonable binding modes in molecular docking were purchased from Specs Company. Eighteen compounds were tested their abilities to enhance ATRA-induced differentiation in human acute promyelocytic leukemia NB4 cells. Eight of them enhanced the ability of ATRA to induce differentiation at concentrations of 0.5 and 1 μM. Among these compounds, 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid (S8) is of most effective in blocking ATRA breaking down in NB4 cells based on the LC-MS/MS assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / chemistry
  • Drug Synergism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemistry
  • Phenylalanine / pharmacology
  • Retinoic Acid 4-Hydroxylase
  • Tretinoin / pharmacology*

Substances

  • 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid
  • Antineoplastic Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Phenylalanine
  • Tretinoin
  • Cytochrome P-450 Enzyme System
  • Retinoic Acid 4-Hydroxylase