Quinoline clubbed triazole hybrids as VEGFR-2 targeted anticancer agents: synthesis, molecular modeling, and...

Targeting tumor angiogenesis through vascular endothelial growth factor receptor-2 (VEGFR-2) remains a promising strategy for breast cancer therapy. In this present research study, a novel series of quinoline-triazole hybrids (SVI01-SVI10) was designed, synthesized, and evaluated as potential VEGFR-2 inhibitors. The compounds were characterized and subjected to molecular docking, MM/GBSA study and MD simulations to investigate their binding affinity and stability within the VEGFR-2 active site (PDB ID: 1Y6A). In vitro cytotoxicity against the MCF-7 breast cancer cell line revealed that compound SVI08 exhibited the moderate activity (IC₅₀ = 13.5 µM), compared to the standard doxorubicin (IC₅₀ = 2.98 µM). Upon docking study, all compounds showed favourable binding interactions with Cys917 in hinge region, along with stable protein-ligand complexes during 100 ns simulations. ADMET profiling indicated acceptable drug-like properties for all compounds. Furthermore, in vivo sub-acute toxicity studies in Wistar rats confirmed that SVI08 is well tolerated up to 50 mg/kg, with no significant histopathological abnormalities. Overall, these findings highlight quinoline-triazole hybrid SVI08 as a preliminary lead to the further optimization as a VEGFR-2-targeted anticancer agents.

The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00728-y.