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

## TL;DR

This study designs and tests new hybrid molecules that show strong anti-inflammatory effects in brain cells, potentially offering new treatments for neurodegenerative diseases.

## Contribution

The paper introduces novel isatin–chalcone hybrid molecules with potent anti-neuroinflammatory activity.

## Key findings

- Compound 4b showed the strongest anti-inflammatory activity with an IC50 of 1.6 μM.
- Compound 4b significantly reduced TNF-α and IL-6 production in microglial cells.
- In silico modeling suggests compound 4b binds to TLR4/MD2 and p38 proteins.

## Abstract

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 4b exhibited the most potent anti-inflammatory activity (IC50 = 1.6 μM; TI = 21.6). After being treated with compound 4b, the production of TNF-α and IL-6 decreased significantly (p < 0.0001). In silico molecular modeling studies on inflammation proteins suggested that compound 4b might bind to TLR4/MD2 and p38. Predicted by the software Molinspiration, the Log p value and Log BB of compound 4b were 3.36 and −0.32, respectively.