Abstract
A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-α-induced monocyte adhesion to colon epithelial cells (an in vitro model of colitis). In TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced rat colitis model, oral administration of the compounds 5b and 5d ameliorated colitis with significant recovery in altered expressions of E-cadherin, TNF-α and IL-1β expressions, indicating 5b and 5d as potential agents for therapeutics development against IBD.
Keywords:
Antiinflammatory agents; Inflammatory bowel disease; Pyridine-linked indanones; Synthesis; TNF-α.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Adhesion / drug effects
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Colitis / chemically induced
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Colitis / drug therapy
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Colitis / pathology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Epithelial Cells / drug effects
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Epithelial Cells / pathology
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HT29 Cells
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Humans
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Indans / administration & dosage
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Indans / chemical synthesis
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Indans / pharmacology*
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Inflammatory Bowel Diseases / drug therapy*
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Inflammatory Bowel Diseases / pathology
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Molecular Structure
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Monocytes / drug effects
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Monocytes / metabolism
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Pyridines / administration & dosage
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Pyridines / chemistry
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Pyridines / pharmacology*
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Rats
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Structure-Activity Relationship
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Trinitrobenzenesulfonic Acid
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Indans
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Pyridines
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Tumor Necrosis Factor-alpha
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Trinitrobenzenesulfonic Acid
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pyridine