Research Information System
ChemistrySelect, vol.11, no.16, 2026 (SCI-Expanded, Scopus)
The development of novel VEGFR-2-targeted anticancer agents remains essential due to the limitations of currently available therapies, including toxicity, resistance, and insufficient selectivity. In this study, a series of 20 oxadiazole-pyrazole hybrid derivatives (BNK-1-20) were rationally designed and synthesized based on key pharmacophoric features of VEGFR-2 inhibitors. The compounds were evaluated for their antiproliferative activity using the MTT assay in A549 (lung), HepG2 (hepatocellular), and MDA-MB-231 (breast) cancer cell lines, along with CCD-34Lu normal fibroblasts to assess selectivity. The results revealed a clear cell-type-dependent response, with HepG2 cells showing the highest sensitivity, followed by A549, while minimal activity was observed in MDA-MB-231 cells. Among the synthesized compounds, BNK-3, BNK-6, BNK-7, and BNK-8 demonstrated the most favorable balance between cytotoxic activity and selectivity, particularly in HepG2 cells. Further investigation of VEGFR-2 protein levels revealed a compound-dependent modulation pattern, in which selected derivatives reduced VEGFR-2 expression, whereas others induced compensatory upregulation. Molecular docking studies supported these findings, showing that compounds with strong VEGFR-2 suppression exhibited favorable binding interactions within the ATP-binding pocket. Overall, these results highlight the potential of oxadiazole-pyrazole hybrids as promising scaffolds for the development of selective VEGFR-2-targeted anticancer agents.