Two series of novel morpholinopyrimidine derivatives were synthesized and screened for their in-vitro cytotoxic activity against 60 tumor cell line by the National Cancer Institute, USA. The in-vitro cytotoxic IC₅₀ values for the most active compounds 6e, 6g, and 6l against the most sensitive cell line leukemia SR were estimated (IC₅₀ = 0.76, 13.59, and 4.37 uM, respectively). To investigate their PI3K enzyme inhibition activity, the assay was done on Class IA (α, β, & δ) isoforms. The IC₅₀ values were very promising: compound [6e = 11.73 (α), 6.09 (β), 11.18 (δ)], compound [6g = 8.43 (α), 15.84 (β), 30.62 (δ)], and compound [6l = 13.98 (α), 7.22 (β), 10.94 (δ)], compared to the reference compound LY294002 = 6.28 (α), 4.51 (β), 4.60 (δ) uM, respectively. Moreover, cell cycle analysis and annexin V-FITC staining were done on Leukemia SR, there was arrest at G2/M phase and apoptosis was induced. Finally, docking study was performed to analyze the interactive mode of these derivatives in PI3Kα ATP-binding site. These outcomes proved that compounds 6e, 6g, and 6l are potential leads for further optimization as antileukemic agents.

合成了两个新的吗啉代嘧啶衍生物系列，并由美国国家癌症研究所筛选了它们对60种肿瘤细胞系的体外细胞毒性活性。在体外的细胞毒性IC ₅₀为最活跃的化合物的值6e中，6克和6升估计针对最敏感的细胞系白血病SR（IC ₅₀  = 0.76，13.59和4.37微米，分别地）。为了研究其PI3K酶抑制活性，对IA类（α，β和δ）同工型进行了测定。IC ₅₀值非常有前途：化合物[ 6e  =  11.73（α），6.09（β），与化合物相比，化合物11.6（δ）]，化合物[ 6g  =  8.43（α），15.84（β），30.62（δ）]和化合物[ 6l  =  13.98（α），7.22（β），10.94（δ）]。参考化合物LY294002 =  6.28（α），4.51（β），4.60（δ）uM。此外，对白血病SR进行细胞周期分析和膜联蛋白V-FITC染色，在G2 / M期停滞并诱导凋亡。最后，进行对接研究以分析这些衍生物在PI3KαATP结合位点的相互作用方式。这些结果证明了化合物6e，6g和6l是作为抗白血病药物进行进一步优化的潜在线索。