Search results for "mPGES-1 inhibitors"

showing 2 items of 2 documents

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

2016

International audience; 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.

0301 basic medicine300323-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors; Biochemistry; Clinical Biochemistry; Molecular Biology; Molecular Medicine; Organic Chemistry; Drug Discovery3003 Pharmaceutical Science; 3003Amino Acid MotifsClinical BiochemistryGene ExpressionPharmaceutical Science01 natural sciencesClinical biochemistryBiochemistry[ CHIM ] Chemical SciencesProtein Structure Secondary[ SDV.CAN ] Life Sciences [q-bio]/Cancerchemistry.chemical_compoundLow affinityDrug DiscoveryEnzyme Inhibitors23-Dihydrobenzofuran privileged structure; Molecular docking; mPGES-1 inhibitors; Cancer; InflammationProstaglandin-E SynthasesCancerAnti-Inflammatory Agents Non-SteroidalBiological activityProto-Oncogene Proteins c-metIntramolecular OxidoreductasesMolecular Docking SimulationMolecular dockingMolecular Medicinelipids (amino acids peptides and proteins)Cell SurvivalStereochemistryMolecular Sequence Data2Antineoplastic Agents[SDV.CAN]Life Sciences [q-bio]/Cancer3-Dihydrobenzofuran privileged structureInhibitory Concentration 50Structure-Activity Relationship03 medical and health sciencesCell Line TumorMicrosomesHumans[CHIM]Chemical SciencesMolecular BiologyBenzofuransInflammationNatural product010405 organic chemistryDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryEpithelial CellsmPGES-1 inhibitorsCombinatorial chemistryCombined approach0104 chemical sciences030104 developmental biologychemistryDrug DesignDrug Screening Assays Antitumor
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Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.

2021

We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…

Molecular modelIn silicoanti-inflammatory drugsanti-inflammatory drugs; anticancer agents; fragment-based approach; mPGES-1 inhibitors; Suzuki-Miyaura cross-coupling01 natural sciences03 medical and health sciencesAcetic acidchemistry.chemical_compoundanticancer agentsQD1-999Suzuki-Miyaura cross-coupling030304 developmental biologyOriginal ResearchA549 cellchemistry.chemical_classification0303 health sciences010405 organic chemistryfragment-based approachmPGES-1 inhibitorsGeneral ChemistryCombinatorial chemistry0104 chemical sciencesChemistryEnzymechemistryApoptosisLead compoundMacromoleculeFrontiers in chemistry
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