Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation

Neuroinflammation is considered a significant factor in triggering numerous neurodegenerative diseases. Hence, the development of effective anti-inflammatory drugs is of utmost urgency. In this study, three series of new isatin-chalcone hybrid derivatives were successfully designed and synthesized, and their anti-neuritis activities were explored using BV2 microglial cells. The results indicated that compound <b>4b</b> exhibited the most potent anti-inflammatory activity (IC₅₀ = 1.6 μM; TI = 21.6). After being treated with compound <b>4b</b>, the production of TNF-α and IL-6 decreased significantly (<i>p</i> < 0.0001). <i>In silico</i> molecular modeling studies on inflammation proteins suggested that compound <b>4b</b> might bind to TLR4/MD2 and p38. Predicted by the software Molinspiration, the Log <i>p</i> value and Log BB of compound <b>4b</b> were 3.36 and -0.32, respectively.