Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking

• Novel series of Indoline ureas (9a–x) was designed and synthesized.
• Anti-proliferative activity of 9a–x was evaluated against HepG2.
• 9n (IC50 = 1.81 ± 0.14 μM) is the most potent derivative against HepG2.
• Inhibitory activity against VEGFR-2 was evaluated for thirteen derivatives.
• Molecular docking was carried out to analyze the binding pattern with VEGFR-2.

In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2-oxoindolin-3-ylidene)amino)phenyl)-3-arylureas was designed and synthesized. All the newly prepared ureas 9a–x were evaluated in vitro for their anti-proliferative activity against HepG2 hepatocellular carcinoma cell line. Compounds 9a–c, 9e, 9f, 9j, 9m–o, 9t–v and 9x exhibited good activity against HepG2 cancer cells (IC50 = 1.22 ± 0.11–8.37 ± 0.85 μM) comparable to that of doxorubicin and sorafinib (IC50 = 2.90 ± 0.36 and 3.40 ± 0.25 μM, respectively). These thirteen compounds were further evaluated for their inhibitory activity against VEGFR-2. Compound 9x emerged as the most active counterpart against VEGFR-2 with IC50 value of 0.31 ± 0.04 μM. Furthermore, a molecular docking of the tested compounds was carried out in order to investigate their binding pattern with the prospective target, VEGFR-2 (PDB-code: 4ASD).

A novel series of indoline ureas 9a–x was designed and synthesized and evaluated for their anti-proliferative activity against HepG2 cancer cell line and for their inhibitory activity against VEGFR-2.Figure optionsDownload as PowerPoint slide