Mitochondria are known as “powerhouse of cells” and play the role of a bridge in redox balance, cell apoptosis, and autophagy. ROS accumulation can cause mitochondria damage, while the injured mitochondria will further enhance ROS levels reciprocally. Herein, we synthesized a novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compounds 4a-4v and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds 4o and 4p inhibited gastric cancer cells at micromolar level. Compound 4o caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound 4o against gastric cancer cell. To our surprising, ROS level was increased by compound 4o and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound 4o in MGC-803 cells. Taken together, compound 4o exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound 4o may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.

线粒体被称为“细胞的动力源”，在氧化还原平衡，细胞凋亡和自噬中起桥梁作用。ROS的积累可引起线粒体损伤，而受伤的线粒体将进一步相互提高ROS水平。在这里，我们合成了一系列新的基于[1,2,4]三唑[1,5 - a ]嘧啶的化合物4a-4v，并测试了它们对胃癌细胞MGC-803的抗增殖作用。其中，化合物4o和4p以微摩尔水平抑制胃癌细胞。化合物4o导致G2 / M停滞并诱导MGC-803和SGC-7901中线粒体依赖性细胞凋亡。但是，抑制细胞凋亡途径不能阻止化合物的抑制活性。4o抗胃癌细胞。令我们惊讶的是，化合物4o增加了ROS的水平，而NAC可以挽救ROS的升高。因此，NAC绝对阻止了化合物4o的抗增殖功效。我们进一步发现自噬抑制剂CQ而非3-MA部分逆转了化合物4o在MGC-803细胞中的抑制活性。总之，化合物4o通过增加ROS水平和诱导自噬而表现出抗增殖活性，从而导致胃癌细胞凋亡。因此，化合物4o可能支持通过线粒体途径进一步开发用于胃癌治疗的先导化合物。