Design, synthesis, molecular docking, and anticancer activity of benzoxazole derivatives as VEGFR-2 inhibitors

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Research

Background:

• Development of novel anticancer agents is crucial for effective cancer therapy.
• Benzoxazole derivatives have shown promise as anticancer agents.
• Targeting vascular endothelial growth factor receptor-2 (VEGFR-2) is a validated strategy in cancer treatment.

Purpose of the Study:

• To design, synthesize, and evaluate a novel series of benzoxazole derivatives for anticancer activity.
• To investigate the inhibitory potential of these compounds against VEGFR-2.
• To explore the structure-activity relationships and binding patterns of these compounds.

Main Methods:

• Synthesis of benzoxazole derivatives (compounds 4a-f to 16).
• In vitro anticancer evaluation against HepG2, HCT-116, and MCF-7 cell lines.
• In vitro evaluation of vascular endothelial growth factor receptor-2 (VEGFR-2) inhibition.
• Molecular docking studies to assess binding affinity and patterns.

Main Results:

• Compound 5e exhibited the most potent anticancer activity across all tested cell lines (HepG2, HCT-116, MCF-7), with IC50 values ranging from 4.13 ± 0.2 µM to 8.67 ± 0.5 µM.
• Several other derivatives (5c, 5f, 6b, 5d, 6c) also displayed significant anticancer activities.
• Compounds 5e and 5c demonstrated potent inhibition of VEGFR-2 with IC50 values of 0.07 ± 0.01 µM and 0.08 ± 0.01 µM, respectively, outperforming sorafenib.

Conclusions:

• The novel benzoxazole derivatives possess significant anticancer potential.
• Compound 5e is a highly promising candidate for further anticancer drug development due to its broad-spectrum activity and potent VEGFR-2 inhibition.
• The study provides a basis for designing more effective VEGFR-2 inhibitors based on the benzoxazole scaffold.