In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (
12d
,
12f
,
12i
,
12l
, and
13a
) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member
12 l (
IC
50
= 10.50 μM and 15.21 μM against HepG2 and MCF-7, respectively
)
had the most promising VEGFR-2 inhibitory activity (IC
50
= 97.38 nM). A further biological evaluation revealed that compound
12l
could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound
12l
could induce apoptosis in HepG2 cells by 35.13%. likely, compound
12l
exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that
12l
exhibited interactions with the key amino acids in a similar way to sorafenib.
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