PI3K pathway has been heavily studied and is one of the most potential targets for various cancer treatment. Herein, we designed and synthesized a series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates contained piperazine based on our previous research. They were evaluated for their PI3Kα wild-type and H1047R mutant inhibitory activities and anticancer effects in vitro. Most of these compounds displayed the potential antiproliferative activities against four cancer cell lines (HCT-116, A549, Huh7 and HL60). Among them, Compound 4p revealed the remarkable antiproliferative activity and was selected for further biological evaluation. Compound 4p displayed the potent activity against both PI3Kα wild-type and H1047R mutant, and a certain degree of selectivity for PI3Kα over PI3Kβ, γ and δ, and meanwhile it can remarkable down-regulate the phosphorylation of Akt. In addition, compound 4p was found to induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. The above results suggested that compound 4p could be considered as a promising PI3Kα inhibitor.

PI3K途径已被大量研究，是各种癌症治疗中最有潜力的靶标之一。在此，根据我们先前的研究，我们设计并合成了一系列新的含哌嗪的chromeno [4,3 - c ] pyrazol-4（2 H）-one衍生物。对它们的PI3Kα野生型和H1047R突变体的抑制活性和体外抗癌作用进行了评估。这些化合物大多数显示出对四种癌细胞系（HCT-116，A549，Huh7和HL60）的潜在抗增殖活性。其中，化合物4p具有显着的抗增殖活性，因此被选择用于进一步的生物学评估。复合4p表现出对PI3Kα野生型和H1047R突变体均有效的活性，并且对PI3Kα对PI3Kβ，γ和δ具有一定程度的选择性，同时可以显着下调Akt的磷酸化。另外，发现化合物4p通过Bax和裂解的半胱天冬酶3/9的上调以及Bcl-2的下调诱导细胞凋亡。以上结果表明化合物4p可以被认为是有希望的PI3Kα抑制剂。