A series of novel 1,2-benzothiazine-1,1-dioxide derivatives (Z)-3- hydroxy-1-(4-hydroxy-2-methyl-1,1-dioxido-2H-benzo[e][1,2] thiazin-3-yl)-3-phenyl substituted prop-2-en-1-one (6a-d) were synthesized starting from sodium salt of saccharin 1 in series of steps via 3-acetyl-2-methyl-1,1-dioxido-2H-benzo[e][1, 2]thiazin- 4-yl substituted benzoates (5a-d). Compound 6e was obtained alternately from 1-(4-Hydroxy-2-methyl-1,1-dioxo-1,2-dihydro- 1l6-benzo[e][1, 2]thiazin-3-yl)-ethanone (4). Compounds 6a-e were further reacted with aromatic azides to form (4-hydroxy-2- methyl-1,1-dioxido-2H-benzo[e][1, 2]thiazin-3-yl)(1-substitutedphenyl)- 5- substituted pheny or methyl-1H-1,2,3-triazol-4-yl) methanone derivatives (7a-o) by regioselective cyclization. All the compounds were evaluated for anti-inflammatory and anticancer activities. Compounds 5a-b, 6a-b, 7a, 7c-d, 7i and 7k-l which showed significant anti-inflammatory activity at micro molar concentration have been identified. Also screened for cytotoxic activity against four human cancer cells and one normal cell such as prostate cancer (PC-3), breast adenocarcinoma (MDA-MB-231), liver hepatocellular carcinoma (Hep G2), cervical cancer (HeLa) and normal umbilical vein endothelial cell (HUVEC). Compounds 6a, 7g, 7h and 7k have been identified as promising candidates. Further, anti-inflammatory activity is also validated by docking studies and compounds 5a, 5b and 7d found to show good interactions when docked with IL-1ss signaling complex.
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