Promoting Apoptosis in MCF-7 Cells via ROS Generation by Quinolino-triazoles Derived from One-Pot Telescopic Synthesis

Inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) facilitates potent antiangiogenic and anticancer responses. In this regard, the development of effective pharmacophores, i.e., quinoline-based triazole derivatives 6a–j, by a one-pot telescopic approach is our focus. Among all of them, 6f, possessing amide and cyanide substituents, displayed the highest binding ability with VEGFR-2, having high affinity of −8.9 kcal/mol. Further, 6f and 6g (containing amide and bromo groups) exhibited a wide spectrum of anticancer activities due to the presence of active oxidative stress inducers, with cytotoxicity values of 10 ± 0.2 and 12 ± 0.6 μM, respectively. Apoptosis analysis demonstrated the involvement of 6f and 6g in mitochondrial damage and the loss of mitochondrial membrane potential (ΔΨ_m). Intercellular localization of 6f/6g in MCF-7 revealed the presence of 6g in the cytoplasm along with an increase in ROS production and a reduction in MMP, proving the ability of 6g to target mitochondria.