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Design and synthesis of 1,3-benzothiazinone derivatives as potential anti-inflammatory agents.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2020 Jun 01; Vol. 28 (11), pp. 115526. Date of Electronic Publication: 2020 Apr 22. - Publication Year :
- 2020
-
Abstract
- A series of 1,3-benzothiazinone derivatives were designed and synthesized for pharmacological assessments. Among the synthesized 19 compounds, some compounds showed high activities on inhibiting LPS-induced nitrite oxide and TNF-α production, down-regulating COX-2 and increasing IL-10 production in RAW264.7 cells. All the compounds had no obvious cytotoxicity in in vitro assay. LD <subscript>50</subscript> value of compound 25 was greater than 2000 mg/kg, which was safer than meloxicam. Compound 25 significantly inhibited phosphorylation of NF-κB and STAT3 in LPS-induced RAW264.7 cells. Inhibition of synthesized compounds on COX activity was weaker than meloxicam. Compound 25 displayed lower gastrointestinal toxicity than meloxicam. Besides, compound 25 decreased the swelling in carrageenan-induced paw edema models of inflammation and reduced PGE <subscript>2</subscript> level significantly. In summary, 1,3-benzothiazinone derivatives are unique scaffolds with anti-inflammatory activity and low toxicity.<br />Competing Interests: Declaration of Competing Interest The authors confirm that this article content has no conflict of interest.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal chemistry
Carrageenan
Cells, Cultured
Dose-Response Relationship, Drug
Edema chemically induced
Edema pathology
Inflammation chemically induced
Inflammation pathology
Lipopolysaccharides antagonists & inhibitors
Lipopolysaccharides pharmacology
Mice
Molecular Structure
NF-kappa B antagonists & inhibitors
NF-kappa B metabolism
Nitric Oxide antagonists & inhibitors
Nitric Oxide biosynthesis
Phosphorylation drug effects
RAW 264.7 Cells
STAT3 Transcription Factor antagonists & inhibitors
STAT3 Transcription Factor metabolism
Structure-Activity Relationship
Thiazines chemical synthesis
Thiazines chemistry
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Drug Design
Edema drug therapy
Inflammation drug therapy
Thiazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 28
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32354672
- Full Text :
- https://doi.org/10.1016/j.bmc.2020.115526