A series of new [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids were designed and synthesized through the scaffold replacement/ring cleavage strategy. SARs studies revealed that the N-heteroarene moiety attached to the thiourea is preferred over the phenyl ring for the R² substituents, while the hydrophobic aromatic group is beneficial for improving the activity. Among these compounds, compound 5r significantly inhibited cell growth of lung cancer cell lines H1650 and A549 (IC₅₀ = 1.91, 3.28 μM, respectively), but was less toxic against the normal cell line GES-1 (IC₅₀ = 27.43 μM). Mechanistic studies showed that compound 5r could remarkably inhibit the colony formation of H1650 cells, induced apoptosis possibly through the intrinsic apoptotic pathways, and arrested the cell cycle at G2/M phase. Our studies suggest that the [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids are a new class of chemotypes possessing interesting antiproliferative activity against lung cancer cells and could be potentially utilized for designing new antitumor agents.

通过支架置换/环裂解策略设计并合成了一系列新的[1,2,3]三唑并[4,5- d ]嘧啶/硫脲杂化物。SARs研究表明，对于R ²取代基，与硫脲连接的N-杂芳基部分比苯环更可取，而疏水性芳香族基团对于改善活性是有利的。在这些化合物中，化合物5r显着抑制肺癌细胞株H1650和A549的细胞生长（分别为IC ₅₀  = 1.91、3.28μM ），但对正常细胞系GES-1的毒性较小（IC ₅₀  = 27.43μM）。机理研究表明，化合物5r可以显着抑制H1650细胞的集落形成，可能通过内在的凋亡途径诱导细胞凋亡，并使细胞周期停滞在G2 / M期。我们的研究表明，[1,2,3]三唑并[4,5- d ]嘧啶/硫脲杂种是一类新型的化学型，对肺癌细胞具有有趣的抗增殖活性，可潜在地用于设计新的抗肿瘤药。