title: 2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors.
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.
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Di Micco
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Spatafora
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Cardullo
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pergola
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koeberle
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: ICMUB, UMR 6302, Université de Bourgogne, 21000 Dijon, France.
authors.forename: Malik
authors.initials: M
authors.lastname: Chalal
authors.affiliation: ICMUB, UMR 6302, Université de Bourgogne, 21000 Dijon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vervandier-Fasseur
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tringali
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy. Electronic address: bifulco@unisa.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
mesh_terms: D020816:Amino Acid Motifs; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D020128:Inhibitory Concentration 50; D019746:Intramolecular Oxidoreductases; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D000071876:Prostaglandin-E Synthases; D017433:Protein Structure, Secondary; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001572:Benzofurans; D004791:Enzyme Inhibitors; D019859:Proto-Oncogene Proteins c-met; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases
keywords: 2,3-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors