New antiproliferative 3-substituted oxindoles inhibiting EGFR/VEGFR-2 and tubulin polymerization

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Research

Background:

• Antiproliferative agents are crucial for cancer therapy.
• Oxindole derivatives represent a promising class of compounds with potential anticancer properties.

Purpose of the Study:

• To design and synthesize novel 3-substituted oxindole derivatives.
• To evaluate the antiproliferative activity of these compounds against a panel of cancer cell lines.
• To investigate the mechanism of action and physicochemical properties of the most potent compounds.

Main Methods:

• Synthesis of 3-substituted oxindole derivatives (compounds 6a-j).
• Antiproliferative activity evaluation against 60 National Cancer Institute (NCI) cell lines.
• In vitro assays for EGFR inhibition and tubulin polymerization.
• In silico molecular docking studies.
• Physicochemical property assessment using the egg-boiled method.

Main Results:

• Compounds 6f and 6g exhibited significant antiproliferative activity, particularly against leukemia and breast cancer.
• Compound 6f showed notable efficacy against MCF-7 cells (IC50 = 14.77 µM) and inhibited EGFR (IC50 = 1.38 µM).
• Compound 6f also demonstrated anti-tubulin polymerization activity (IC50 = 7.99 µM) and favorable physicochemical properties for drug development.

Conclusions:

• Novel 3-substituted oxindole derivatives possess promising antiproliferative potential.
• Compound 6f is a lead candidate for further development as an anticancer agent, targeting EGFR and tubulin polymerization.
• The favorable physicochemical profile of compound 6f supports its potential for good absorption and distribution in vivo.