Abstract
Compounds 8h, 8l, and 8r exhibited strong antitumor activity against the used tumor cell lines. Compounds 8h, and 8l displayed the highest inhibitory activity against VEGFR-2 (IC50 = 60.27 and 93.5 nM, respectively), also compared to the reference drug sorafenib (IC50 = 55.43 nM). Compound 8h induced apoptosis at the Pre-G phase and cell cycle arrest at the G2/M phase in the MCF-7 cells.
[Display omitted]
•Antitumor activity of 2-vinylquinazolines was tested against three cancer cell lines.•Compounds 8 h, 8 l, and 8r showed potential antitumor activities.•Compound 8 h showed the most potent inhibitory activity against VEGFR-2.•Compound 8 h induced apoptosis and showed cell cycle arrest at the G2/M phase.•Molecular docking into VEGFR-2 was performed for compound 8 h.
The antitumor activity of newly synthesized 4-anilino-2-vinylquinazolines 8a-r was measured comparable to sorafenib as a standard drug. The 2-vinylquinazolines 8a-r were evaluated for their in vitro antitumor activity. The most active antitumor agents were subjected to in vitro VEGFR-2 inhibition and apoptotic inducing assay. Compounds 8 h, 8 l, and 8r showed potential antitumor activities with IC50 values of 4.92–14.37 μM relative to the reference drug, sorafenib (IC50 values of 5.47–9.18 μM). Compound 8 h possessed potential VEGFR-2 inhibitory activity (IC50 = 60.27 nM) compared to standard drug sorafenib (IC50 = 55.43 nM), whereas compound 8 l showed moderate inhibitory activity (IC50 = 93.50 nM). The most active compound, 8 h, exhibited total apoptosis with 36.24% on MCF-7 cells, more than the apoptotic effect provoked by sorafenib (32.46%) and the cell cycle arrested at a G1/S phase. Compound 8 h, a potent VEGFR-2 inhibitor, was docked into the VEGFR-2 binding pocket, where this compound showed binding interaction similar to co-crystallized inhibitor sorafenib.