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

Simone Di Micco; Carmela Spatafora; Nunzio Cardullo; Raffaele Riccio; Katrin Fischer; Carlo Pergola; Andreas Koeberle; Oliver Werz; Malik Chalal; Dominique Vervandier-Fasseur; Corrado Tringali; Giuseppe Bifulco

doi:10.1016/j.bmc.2016.01.002

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.

Affiliations

¹ Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.
² Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
³ Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
⁴ ICMUB, UMR 6302, Université de Bourgogne, 21000 Dijon, France.
⁵ Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy. Electronic address: bifulco@unisa.it.

PMID: 26777299
DOI: 10.1016/j.bmc.2016.01.002

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