Synthesis Of Novel Isoflavone/Benzo-Delta-Sultam Hybrids As Potential Anti-Inflammatory Drugs

A small series of novel isoflavone/benzo-o-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-o-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-alpha production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-alpha to 34% at 20 mu M final concentration in the well.