Abstract
A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.
Keywords:
Anti-inflammatory; Isoflavone; Microglia; TNF-α; δ-sultam.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Line
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Dose-Response Relationship, Drug
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Isoflavones / chemistry
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Isoflavones / pharmacology*
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Mice
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Microglia / drug effects*
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Microglia / metabolism
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Molecular Structure
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Nitric Oxide / antagonists & inhibitors*
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Nitric Oxide / biosynthesis
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Structure-Activity Relationship
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Isoflavones
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Lipopolysaccharides
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Sulfonamides
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Tumor Necrosis Factor-alpha
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beta-sultam
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Nitric Oxide