In this paper, based on molecular hybridization, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazine was synthesized and their antiproliferative activities against 5 cancer cell lines (MGC-803, PC3, PC9, EC9706 and SMMC-7721) were evaluated. We found that most of them exhibited obvious growth inhibition effects on these tested cancer cells, especially compound 34 on PC3 cells (IC₅₀ = 26.25 ± 0.28 nM). Meanwhile, compound 34 displayed best selectivity on PC3, compared with the other cancer cell lines, as well as excellent selectivity towards normal cell lines (Het-1A, L02 and GES-1). Further investigations demonstrated that 34 could significantly inhibit PC3 cells’ colony formation, increase cellular ROS content, suppress EGFR expression and induce apoptosis. Our findings indicate that 34 may serve as a novel lead compound for the discovery of more triazolopyrimidine derivatives with improved anticancer potency and selectivity.

本文在分子杂交的基础上，合成了一系列含肼的[1,2,3]三唑并[4,5- d ]嘧啶衍生物，并对5种癌细胞系（MGC-803，PC3，PC9）具有抗增殖活性。 （EC9706和SMMC-7721）进行了评估。我们发现它们中的大多数对这些经过测试的癌细胞，特别是化合物34对PC3细胞表现出明显的生长抑制作用（IC ₅₀  = 26.25±0.28 nM）。同时，与其他癌细胞系相比，化合物34在PC3上表现出最佳的选择性，并且对正常细胞系（Het-1A，L02和GES-1）的选择性也极好。进一步的调查表明34能够显着抑制PC3细胞集落形成，增加细胞ROS含量，抑制EGFR表达并诱导细胞凋亡。我们的发现表明34可以作为一种新型的先导化合物，用于发现更多具有改善的抗癌效力和选择性的三唑并嘧啶衍生物。