Design, synthesis, and anti-tumor evaluation of indolin-2-one derivatives based on 3D-QSAR.

Tropomyosin receptor kinase (TRK) plays a critical role in tumorigenesis, and its aberrant activation is strongly implicated in cancer progression and metastasis. In this study, a series of novel indoline-2-one derivatives were designed and synthesized using a 3D-QSAR-guided approach targeting TRK. The antitumor potential of these compounds was evaluated through a panel of in vitro bioassays. Several derivatives were found to reduce TRK phosphorylation levels in a cellular context and exhibited pronounced anti-proliferative and anti-migratory effects. Among them, compound IIIc demonstrated potent activity against HepG2 hepatocellular carcinoma cells, with an IC₅₀ value of 2.06 μM. Furthermore, ELISA-based phosphorylation assays revealed that treatment with compound IIIc resulted in decrease in TRK phosphorylation, yielding an IC₅₀ of 0.19 μM, highlighting its therapeutic promise. Collectively, this study provides experimental evidence and a structural basis for the development of lead compounds capable of modulating TRK signaling in cancer therapy.