Synthesis and biologic activity studies of some substitued n-(1,3-dioxohexahydro-2h-isoindol-2-yl)benzenesulfonamide derivatives

In the course of this study five out of ten novels substitued N-(1,3-dioxohexahydro-2H-isoindol-2-yl)benzenesulfonamide (compound 1-10) were synthesized byusing two different methods. In the first method, the cis-1,2-cyclohexanecarboxylic anhydride and sulfa derivatives were conventionally heated in acetic acid for 4 hours In the second method, the cis-1,2-cyclohexanecarboxylic anhydride and sulfa derivatives were dissolved in DMF and radiated by microwave. Structure elucidation of the synthesized compounds were confirmed by UV, IR 1H-NMR,13C-NMR with mass spectral methods. Anticancer activities of the compounds were studied on human breast cancer (MCF7) cell lines by MTT assay. Anti-inflammatory activities of the compounds were examined by measuring nitrite concentrations by using a colorimetric method based on the Griess reaction on RAW 264.7 macrophage cells. Synthesized compounds generally showed moderate or no cytotoxic activity against MCF7 cell line. Among them, 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)benzenesulfonamide (compound 3), 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(4,5-dimethoxypyrimidin-2-yl)benzenesulfonamide (compound 7), and 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (compound 10) presented activity against MCF7 cancer cell lines with IC50 values of 87.9  2.34 μM, 71.5  3.01 μM, and 89.3  2.05 μM, respectively. Proposed compounds were also analyzed for their anti-inflammatory activity on RAW 264.7 macrophage cells. Among them, 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(6-mmethoxypyridazin-3-yl)benzenesulfonamide (compound 4), 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide (compound 1) and 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)benzenesulfonamide (compound 9) presented activity against RAW 264.7 macrophages with NO inhibition (% of control) values of 24.43  3.16 μM, 9.73  1.04 μM and 6.44  2.48 μM, respectively. No significant cytotoxic activities on RAW 264.7 macrophage cells were observed under all tested concentrations and IC50 values of the tested compounds were higher than 500 μM. Compounds 1-10 Figure 1: Structures of the synthesized compounds (1-10)