WITHDRAWN: Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Oncology

Background:

• Human esophageal squamous cell carcinoma (ESCC) presents a significant health challenge due to its high mortality rate and limited treatment options.
• Indoline scaffolds have emerged as promising fragments for the development of novel anticancer therapeutics.
• There is a critical need for innovative antitumor agents to improve outcomes for patients with esophageal cancers.

Purpose of the Study:

• To design and synthesize novel indoline derivatives.
• To evaluate the anticancer activity of these synthesized compounds.
• To identify potential tubulin inhibitors for ESCC treatment.

Main Methods:

• Chemical synthesis of indoline derivatives.
• In vitro antiproliferative activity assays against various cancer cell lines.
• Identification of the mechanism of action, including tubulin polymerization inhibition.
• Molecular docking studies to assess binding affinity to the colchicine binding site of β-tubulin.
• Time- and dose-dependent growth inhibition assays.

Main Results:

• Compound 9d demonstrated potent antiproliferative activity across multiple cancer cell lines, with IC50 values as low as 1.49 μM.
• Compound 9d was identified as a tubulin inhibitor targeting the colchicine binding site, with an IC50 of 3.4 μM.
• The compound effectively suppressed tubulin polymerization in Kyse450 cells.
• Molecular docking confirmed strong binding of compound 9d to the β-tubulin colchicine binding site.
• Compound 9d exhibited time- and dose-dependent inhibition of KYSE450 cell growth.

Conclusions:

• Indoline derivatives represent a promising class of novel tubulin inhibitors.
• Compound 9d shows significant potential as an anticancer agent for esophageal squamous cell carcinoma.
• Further investigation into these indoline derivatives is warranted for their therapeutic development.