Development of novel indazolyl-acyl hydrazones as antioxidant and anticancer agents that target VEGFR-2 in human breast cancer cells

The increased expression of VEGFR-2 in a variety of cancer cells promotes a cascade of cellular responses that improve cell survival, growth, and proliferation. Heterocycles are common structural elements in medicinal chemistry and commercially available medications that target several biological pathways and induce cell death in cancer cells. Herein, the evaluation of indazolyl-acyl hydrazones as antioxidant and anticancer agents is reported. Compounds 4e and 4j showed inhibitory activity in free radical scavenging assays (DPPH and FRPA). The titled compounds were employed in cell viability studies using MCF-7 cells, and it was observed that compounds 4f and 4j exhibited IC₅₀ values 15.83 μM and 5.72 μM, respectively. In silico docking revealed the favorable binding energies of -7.30 kcal/mol and -8.04 kcal/mol for these compounds towards Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), respectively. In conclusion, compounds with antioxidant activity and that target VEGFR-2 in breast cancer cells are reported.