Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative...

Area of Science:

• Medicinal Chemistry
• Cancer Research
• Pharmacology

Background:

• Developing novel anticancer agents is crucial for improving patient outcomes.
• Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) is a key target in cancer therapy.
• Previous research identified promising VEGFR-2 inhibitor candidates.

Purpose of the Study:

• To synthesize and evaluate new benzoxazole-based compounds as potential anticancer agents.
• To assess the inhibitory activity of these compounds against human cancer cell lines and VEGFR-2 kinase.
• To investigate the mechanism of action of the most potent compounds.

Main Methods:

• Synthesis of thirteen novel benzoxazole derivatives.
• In vitro evaluation against human breast (MCF-7), colorectal (HCT116), and hepatocellular (HepG2) carcinoma cell lines.
• In vitro assessment of VEGFR-2 kinase inhibition activity.
• Apoptosis assays and cell cycle analysis.
• Molecular docking studies.

Main Results:

• Compound 8d exhibited superior cytotoxic effects against all tested cancer cell lines compared to sorafenib.
• Compound 8d demonstrated enhanced inhibition of VEGFR-2 kinase activity.
• Compounds 8a and 8e also showed significant VEGFR-2 inhibition.
• Compound 8d induced apoptosis and cell cycle arrest at the pre-G1 phase in HepG2 cells.
• Molecular docking confirmed a similar binding pattern of the new compounds to VEGFR-2 as sorafenib.

Conclusions:

• The novel benzoxazole derivatives, particularly compound 8d, represent promising candidates for anticancer drug development.
• Compound 8d's potent activity against multiple cancer cell lines and VEGFR-2 inhibition warrants further investigation.
• The findings support the development of benzoxazole-based VEGFR-2 inhibitors for cancer therapy.