Synthesis and Biological Activity Studies of Substituted N-(1,3-Dioxohexahydro-2H-Isoindol-2-yl) Benzenesulfonamide Derivatives

Abstract In this study, ten substituted N – ([1,3-dioxoindolin-2-yl] phenyl] sulfonyl) structures (compound 1-10), which seven of them were original synthesized using conventional and microwave synthesis methods.  In the first method the cis-1,2-cyclohexanecarboxylic anhydride and sulfa derivatives reacted under  reflux for 2-3 hours in acetic acid. 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 and elemental analysis method. Anticancer activities of the compounds were studied by MTT assay. Synthesized compounds generally showed moderate or no cytotoxic activity against MCF7 (human breast cancer cell line). Among them, N-([1,3-Dioxoindolin-2-yl)phenyl]sulfonyl)6-amino-4,5-dimethoxypyrimidine (7), N-([1,3-Dioxoindolin-2-yl)phenyl]sulfonyl)-2-aminothiazole (3) and N-([1,3-Dioxoindolin-2-yl)phenyl]sulfonyl)aminopyrimidine (10) presented activity against MCF7 cancer cell lines with IC50 values of 71.5 ± 3.01μM,  87.9 ± 2.34and 89.3 ± 2.05 μM, respectively. Anti-inflammatory activity of the compounds were tested against LPS-induced nitrite production in RAW 264.7cell line. The compounds4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(5-methyl-1,2-oxazol-3-yl) benzenesulfonamide(1), 4-(1,3-dioxohexahydro-2H-isoindol-2-yl)-N-(6-methoxypyridazin-3-yl)benzenesulfonamide (4) and 4-(1,3-Dioxohexahydro-2H-isoindol-2-yl)benzenesulfonamide (9) showed nitrite production inhibitory activity 24.43 ± 3.16, 9.73 ± 1.04, and 6.44 ± 2.48 µM, respectively. Compound 4 exhibited the highest anti-inflammatory activity by suppressing the NO production. These compounds might be candidate to inflammatory therapy for further development.

Keywords Anticancer activity, Anti-inflammatory activity, Breast cancer MCF-7, Pharmaceutical analysis.

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Updated: January 20, 2024 — 8:21 am