Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

中文翻译：

---

硒化咪唑并 [1,2-a] 吡啶诱导慢性粒细胞白血病细胞的细胞衰老和氧化应激。

咪唑并 [1,2-a] 吡啶 (IPs) 已在药物开发方面进行了研究。这项工作的目的是通过筛选 IP 衍生物作为促氧化剂的能力来评估 IP 衍生物的抗白血病能力。合成了 IP 衍生物，并在计算机上分析了口服生物利用度和毒性。对人类 Kasumi、KG-1、K562 和 Jurkat 白血病细胞进行氧化还原筛选。选择 IP 衍生物和反应最灵敏的白血病细胞进行细胞毒性、细胞增殖、细胞衰老和氧化应激测定。预测性毒性分析表明可能对生殖系统产生影响，但没有致突变、致癌或易激惹的影响。针对 K562 细胞的 MRK-107 是显示最佳氧化还原曲线的化合物。MRK-107 不会在 K562 和单核细胞中诱导细胞死亡。然而，该化合物能够在 48 和 72 小时后减少细胞增殖并增加细胞衰老。此外，MRK-107 在 72 小时后在 K562 细胞中诱导氧化应激，增加脂质过氧化并降低还原型谷胱甘肽 (GSH) 含量。这项研究表明，MRK-107 诱导的衰老与氧化应激的参与是一种可能的作用机制，将这种化合物作为一种潜在的抗慢性粒细胞白血病的抗肿瘤药物。