The discovery and development of effective novel compounds is paramount in oncology for improving cancer therapy. In this study, we developed a new derivative of spiroindolone (7’,8’-Dimethoxy-1’,3’-dimethyl-1,2,3’,4’-tetrahydrospiro[indole-3,5’- pyrazolo[3,4-c]isoquinolin]-2-one) and evaluated its anticancer- and immunomodulatory potential in a vitro model of chronic leukemia. We utilized the chronic leukemia cell line K562, as well as non-cancerous peripheral blood mononuclear cells (PBMC) and Vero cells (kidney epithelium of Cercopithecus aethiops). We assessed the cytotoxicity of the compound using the MTT assay, and performed cell cycle assays to determine its impact on different stages of the cell cycle. To evaluate its antineoplastic activity, we conducted a colony formation test to measure the effect of the compound on the clonal growth of cancer cells. Furthermore, we evaluated the immunomodulatory activity of the compound by measuring the levels of pro and anti-inflammatory cytokines. The study findings demonstrate that the spiroindolone-derived compound exerted noteworthy cytotoxic effects against K562 cells, with an IC50 value of 25.27 µg/mL. Additionally, it was observed that the compound inhibited the clonal proliferation of K562 cells while displaying minimal toxicity to normal cells. The compound exhibited its antiproliferative activity by inducing G2/M cell cycle arrest, preventing the entry of K562 cells into mitosis. Notably, the compound demonstrated an immunomodulatory effect by upregulating the production of cytokines IL-6 and IL-12/23p40. In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications.

有效的新型化合物的发现和开发对于改善癌症治疗在肿瘤学中至关重要。在这项研究中，我们开发了一种新的螺吲哚酮衍生物（7',8'-Dimethoxy-1',3'-二甲基-1,2,3',4'-四氢螺[indole-3,5'-吡唑并[3]） ,4-c]异喹啉]-2-一）并评估其在慢性白血病体外模型中的抗癌和免疫调节潜力。我们使用慢性白血病细胞系 K562，以及非癌性外周血单核细胞 (PBMC) 和 Vero 细胞（Cercopithecus aethiops 的肾上皮）。我们使用 MTT 测定评估了该化合物的细胞毒性，并进行了细胞周期测定以确定其对细胞周期不同阶段的影响。为了评估其抗肿瘤活性，我们进行了集落形成试验，以测量该化合物对癌细胞克隆生长的影响。此外，我们通过测量促炎细胞因子和抗炎细胞因子的水平评估了该化合物的免疫调节活性。研究结果表明，螺吲哚酮衍生化合物对 K562 细胞具有显着的细胞毒性作用，IC50 值为 25.27 µg/mL。此外，还观察到该化合物抑制 K562 细胞的克隆增殖，同时对正常细胞的毒性最小。该化合物通过诱导 G2/M 细胞周期停滞、阻止 K562 细胞进入有丝分裂来展现其抗增殖活性。值得注意的是，该化合物通过上调细胞因子 IL-6 和 IL-12/23p40 的产生表现出免疫调节作用。总之，本研究中评估的螺吲哚酮衍生化合物已显示出作为治疗慢性粒细胞白血病的治疗剂的巨大潜力。需要进一步研究以探索其临床应用。