Design, Synthesis, and Anti-Tumor Activity Evaluation In Vitro of 4,6,7–Trisubstituted Quinazoline Derivatives Containing Acrylamide Group

Objective: In order to enrich the library of anti-tumor small molecule compounds, 19 compounds, with highly effective anti-tumor, have been designed and synthesized. Methods: MTT assay was used to detect the anti-proliferation activity of 19 compounds on four human tumor cell lines (PC-3, H1975, A549 and Eca-109). Cell cycle experiment, cell migration experiment, cell clone experiment and cell apoptosis experiment were used to study the anti-tumor mechanism of compound (XIVm). Results: The compound (XIVm) showed the strongest anti-tumor activity against the above four human tumor cells, especially against H1975 cells, with an IC50 value of 1.09 ± 0.04 μM, which was significantly lower than that of 5-fluorouracil (5-FU). The results of a variety of cell experiments showed that the compound (XIVm) significant anti-tumor activity, such as inhibiting the proliferation and migration of H1975 cells, arresting H1975 cells at G2/M phase, and inducing apoptosis in H1975 cells. Discussion: Slight changes in the R group can cause significant changes in the in vitro anti-tumor activity. And when R is a strong electron withdrawing group of cyano and trifluoromethyl, compound (XIVm) exhibits the strongest inhibitory effect, with an IC50 value of 1.09 ± 0.04 μM on H1975 cells. Conclusions: 19 compounds showed significant anti-tumor activity, and the compound (XIVm), with a strong electron withdrawing group of cyano and trifluoromethyl, showed the most significant effect, and the anti-proliferation and anti-migration effects of compound (XIVm) was further investigated.