Assessment of thiosemicarbazone‐containing compounds as potential anti‐leukemia agents against P‐gp overexpressing drug resistant K562/A02 cells,Chemistry & Biodiversity

当前位置： X-MOL 学术 › Chem. Biodivers. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Assessment of thiosemicarbazone‐containing compounds as potential anti‐leukemia agents against P‐gp overexpressing drug resistant K562/A02 cells
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2021-01-12 , DOI: 10.1002/cbdv.202000775
Xiaoke Gu ₁ , Mingyu Guan ₁ , Chunyu Jiang ₁ , Qinghua Song ₁ , Xin Li ₁ , Nan Sun ₁ , Jing Chen ₁ , Jingying Qiu ₁

Affiliation

P-glycoprotein (P-gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone-containing compounds were prepared and evaluated as potential anti-leukemia agents against drug resistant K562/A02 cell overexpressing P-gp. Among them, ( E )- N -hydroxy-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)hexanamide could significantly inhibit K562/A02 cells proliferation with an IC 50 value of 0.96 μM. Interestingly, ( E )- N -hydroxy-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)hexanamide could dose-dependently increase ROS levels of drug resistant K562/A02 cells, thus displaying a potential collateral sensitivity (CS)-inducing effect and selectively killing K562/A02 cells. Furthermore, ( E )- N -hydroxy-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)hexanamide possessed potent inhibitory effect on HDAC1 and HDAC6, and could promote K562/A02 cells apoptosis via dose-dependently increasing Bax expression, reducing Bcl-2 protein level, and inducing the cleavage of PARP and caspase3. These present findings suggest that ( E )- N -hydroxy-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)hexanamide might be a promising lead to discover novel anti-leukemia agents against P-gp overexpressing leukemic cells.

中文翻译：

评估含有氨基硫脲的化合物作为抗 P-gp 过表达耐药 K562/A02 细胞的潜在抗白血病药物

P-糖蛋白（P-gp）过度表达被认为是白血病多药耐药（MDR）和化疗失败的主要原因。在这项研究中，制备了 17 种含缩氨基硫脲的化合物，并将其评估为潜在的抗白血病药物，以对抗过度表达 P-gp 的耐药性 K562/A02 细胞。其中，(E)-N-羟基-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)己酰胺能显着抑制K562/A02细胞增殖，IC 50 值为0.96 μM。有趣的是，(E)-N-羟基-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)hexanamide 可以剂量依赖性地增加耐药 K562/A02 细胞的 ROS 水平，从而显示出潜在的附带敏感性（CS )-诱导作用和选择性杀死 K562/A02 细胞。此外，( E )- N-hydroxy-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)己酰胺对HDAC1和HDAC6具有强效抑制作用，可通过剂量依赖性增加Bax表达促进K562/A02细胞凋亡，降低 Bcl-2 蛋白水平，并诱导 PARP 和 caspase3 的裂解。目前的这些发现表明 (E)-N-羟基-6-(2-(3-nitrobenzylidene)hydrazine-1-carbothioamido)己酰胺可能是发现针对 P-gp 过表达白血病细胞的新型抗白血病药物的有希望的线索。

更新日期：2021-01-12

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11