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

  • Bioorg Med Chem Lett. 2026 Jul:136:130618. doi: 10.1016/j.bmcl.2026.130618.
Xingdan Wang  1 ,  Liying Zhang  1 ,  Ziqi He  1 ,  Xinyue Li  1 ,  Jing Bai  2 ,  Qidi Zhong  3
Affiliations
  • 1. School of Pharmacy, North China University of Science and Technology, Tangshan 063210, China.
  • 2. School of Basic Medicine, North China University of Science and Technology, Tangshan 063210, China. Electronic address: [email protected].
  • 3. School of Pharmacy, North China University of Science and Technology, Tangshan 063210, China. Electronic address: [email protected].
PMID: 41825650 DOI: 10.1016/j.bmcl.2026.130618
Abstract

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.

Keywords
3D-QSAR; Antitumor activity; Indolin-2-one derivatives; Molecular docking.
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