开发新的、有效的乳腺癌治疗药物仍然是肿瘤学的首要任务。这种病理学的治疗策略很大程度上取决于人类乳腺癌细胞的基因型和表型。我们的目的是研究新型吡咯烷二酮-噻唑烷酮杂合分子 Les-6287、Les-6294 和 Les-6328 对不同类型人乳腺癌细胞 MDA-MB-231、MCF-7、T-47D 和 T-47D 的抗肿瘤活性。使用 MTT、克隆形成和 [3H]-胸苷掺入测定、流式细胞术、ELISA 和 qPCR 对 HCC1954 系和鼠乳腺癌 4T1 细胞进行分析。研究的杂交体对上述肿瘤细胞具有毒性，IC50 范围为 1.37 至 21.85 µM。同时，这些衍生物对 MCF-10A 系的假正常人乳腺上皮细胞显示出低毒性 (IC50 > 93.01 µM)。 1 µM 的 Les-6287 完全抑制 MCF-7、MDA-MB-231 和 HCC1954 细胞集落的形成，而 Les-6294 和 Les-6328 分别在 2.5 和 5 µM 时发挥作用。 Les-6287 抑制 MCF-7、MDA-MB-231 和 HCC1954 细胞中的 DNA 生物合成。同时，这种对MCF-10A细胞的影响明显较低。 Les-6287 通过降低线粒体膜电位，利用外在和内在途径诱导细胞凋亡，从而增加所有免疫组织化学不同的人乳腺癌细胞中半胱天冬酶 3/7、8、9 和 10 的活性。 Les-6287 降低了转移和侵袭相关蛋白 MMP-2、MMP-9 和 ICAM-1 的浓度。它不会在处理的细胞中诱导自噬。总之，我们的研究结果表明，合成的杂化吡咯烷二酮-噻唑烷酮可能是治疗不同类型乳腺肿瘤的有前途的药物。

The development of new, effective agents for the treatment of breast cancer remains a high-priority task in oncology. A strategy of treatment for this pathology depends significantly on the genotype and phenotype of human breast cancer cells. We aimed to investigate the antitumor activity of new pyrrolidinedione-thiazolidinone hybrid molecules Les-6287, Les-6294, and Les-6328 towards different types of human breast cancer cells of MDA-MB-231, MCF-7, T-47D, and HCC1954 lines and murine breast cancer 4T1 cells by using the MTT, clonogenic and [3H]-Thymidine incorporation assays, flow cytometry, ELISA, and qPCR. The studied hybrids possessed toxicity towards the mentioned tumor cells, with the IC50 ranging from 1.37 to 21.85 µM. Simultaneously, these derivatives showed low toxicity towards the pseudonormal human breast epithelial cells of the MCF-10A line (IC50 > 93.01 µM). Les-6287 at 1 µM fully inhibited the formation of colonies of the MCF-7, MDA-MB-231, and HCC1954 cells, while Les-6294 and Les-6328 did that at 2.5 and 5 µM, respectively. Les-6287 suppressed DNA biosynthesis in the MCF-7, MDA-MB-231, and HCC1954 cells. At the same time, such an effect on the MCF-10A cells was significantly lower. Les-6287 induces apoptosis using extrinsic and intrinsic pathways via a decrease in the mitochondrial membrane potential, increasing the activity of caspases 3/7, 8, 9, and 10 in all immunohistochemically different human breast cancer cells. Les-6287 decreased the concentration of the metastasis- and invasion-related proteins MMP-2, MMP-9, and ICAM-1. It did not induce autophagy in treated cells. In conclusion, the results of our study suggest that the synthesized hybrid pyrrolidinedione-thiazolidinones might be promising agents for treating breast tumors of different types.