2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors

Bioorg Med Chem. 2016 Feb 15;24(4):820-6. doi: 10.1016/j.bmc.2016.01.002. Epub 2016 Jan 4.

Abstract

2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.

Keywords: 2,3-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzofurans / chemical synthesis*
  • Benzofurans / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology
  • Gene Expression
  • Humans
  • Inhibitory Concentration 50
  • Intramolecular Oxidoreductases
  • Microsomes / drug effects*
  • Microsomes / enzymology
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Prostaglandin-E Synthases
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / chemistry
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Benzofurans
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-met
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases