Design and synthesis of 1,3-benzothiazinone derivatives as potential anti-inflammatory agents.

Design and synthesis of 1,3-benzothiazinone derivatives as potential anti-inflammatory agents. Bioorg Med Chem. 2020 Apr 22;:115526 Authors: Li J, Fan X, Deng J, Liang Y, Ma S, Lu Y, Zhang J, Shi T, Tan W, Wang Z 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. LD50 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 PGE2 level significantly. In summary, 1,3-benzothiazinone derivatives are unique scaffolds with anti-inflammatory activity and low toxicity. PMID: 32354672 [PubMed - as supplied by publisher]
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research