Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and Cytotoxicity.

New derivatives -, , -, -, , , , -, -, and were synthesized and evaluated for their VEGFR-2 inhibition. Compounds , , and showed remarkable enzyme inhibition IC = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 cancer cell lines in addition to WI-38. Compound displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC = 6.66 and 8.51 μM) compared to sorafenib (IC = 6.60 and 8.78 μM). Cell cycle analysis and apoptotic assay of in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of apoptosis. Western blot analysis of compound revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of showed inhibition of wound closure. Additionally, molecular modeling studies of compounds , , and were carried out.