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首页> 外文期刊>Life sciences >Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-((3-nitrophenoxy) methyl)-2,2-dimethyloxazolidine-3-carboxylate.
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Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-((3-nitrophenoxy) methyl)-2,2-dimethyloxazolidine-3-carboxylate.

机译：针对白血病细胞的细胞毒性和促凋亡化合物的发现：4-（（3-硝基苯氧基）甲基）-2,2-二甲基恶唑烷-3-羧酸叔丁酯。

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AIMS: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3-carboxylate (BNDC). MAIN METHODS: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide-PI staining) and phosphatidylserine exposure (Annexin-V and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD-FMK, a non-selective caspase inhibitor, by flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry. KEY FINDINGS: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell--PBMC based on IC50 values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after treatment with compounds. SIGNIFICANCE: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro-apoptotic activities and have a potential for developing a new class of anticancer drugs.
机译：目的：我们评估了4-[（（3-硝基苯氧基）-甲基] -2,2-二甲基恶唑烷-3-羧酸叔丁酯（BNDC）的R和S对映异构体在白血病细胞系中的生物活性。主要方法：细胞毒性活性通过MTT分析评估。流式细胞术测定法用于确定DNA片段化（碘化丙啶-PI染色）和磷脂酰丝氨酸暴露（膜联蛋白-V和PI染色）。通过在白血病细胞（Hoechst和PI）中使用双重染色的荧光显微镜对DNA缩合进行评估。使用非选择性caspase抑制剂Z-VAD-FMK通过流式细胞术和使用选择性caspase-3底物Z-DEVD-AMC通过荧光光谱法测量caspase活性。主要发现：两种对映异构体均对白血病细胞系（HL60，HL60.Bcl-2，HL60.Bcl-XL和Jurkat）表现出细胞毒活性，基于IC50值对人外周血单个核细胞PBMC的毒性较低。在HL60细胞系中，化合物诱导磷脂酰丝氨酸的暴露和DNA片段化，这可以通过用Z-VAD-FMK预处理细胞来阻止。证实该观察结果，两种对映异构体均诱导caspase-3活化。进一步的分析显示，用化合物处理后，凋亡细胞（定义为具有破碎的核和染色质浓缩的细胞）的百分比增加。总计：结果表明，BNDC化合物具有细胞毒性和促凋亡活性，并具有开发新型抗癌药物的潜力。

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