PDF(Pubmed)
Abstract：
Glioblastoma multiforme (GBM) is the most common and primary brain tumor with poor prognosis. They are removed by following tedious and life threatening surgeries. GBM stem cells (GSCs) are the main source of tumor recurrence after surgery. Hence, drugs are designed to overcome the recurrent glioblastoma malignant cells. Currently used chemotherapies are not cost effective as well as bear resistance. New and effective chemotherapeutic compounds are developed to overcome the intrinsic and acquired resistance. Dicoumarol derivative 3,3\'-[(4-methoxyphenyl)methanediyl]bis(4-hydroxy-2Hchromen-2-one) (HL) and its triethylammonium salt triethylammonium3-[(4-methoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2-oxo-2H-chromen-4-olate (L) were synthesized and characterized using spectral and analytical techniques. The deprotonated compound L was further studied structurally using single crystal analysis. Cytotoxic studies against human glioblastoma cells A172 and LN229 were investigated both dose and time dependently and compared with the cytotoxicity of normal human astrocytes (NHA). The IC50 value of HL against A172 was found to be lying within the range 2.68-0.95 μM whereas against LN229 the range was found to be 9.55-0.85 μM. Similarly, the compound L revealed range of 1.9-0.271 μM against A172 and 1.2-0.27 μM against LN229. Cell cycle arrest was observed in GBM cells treated with L compared to the control group, which suggested that L may trigger apoptosis in GBM cells according to cytotoxicity and flow cytometry results. The antioxidant activity of synthesized compounds was also investigated using DPPH free radicals.
摘要：
多形性胶质母细胞瘤（GBM）是最常见的原发性脑肿瘤，预后较差。通过繁琐且危及生命的手术将其移除。GBM干细胞(GSCs)是肿瘤术后复发的主要来源。因此，药物旨在克服恶性胶质母细胞瘤的复发。目前使用的化学疗法不具有成本效益，并且具有耐药性。开发新的和有效的化疗化合物来克服内在和获得性抗性。双香豆酚衍生物3,3'-[(4-甲氧基苯基)甲二基]双(4-羟基-2Hchromen-2-one)(HL)及其三乙基铵盐三乙基铵盐-3-[(4-甲氧基苯基)(4-羟基-2-氧代-2H-色烯-3-基)甲基]-2-氧代-2H-色烯-4-(L)进行了合成和分析使用单晶分析进一步在结构上研究去质子化的化合物L。剂量和时间依赖性地研究了针对人胶质母细胞瘤细胞A172和LN229的细胞毒性研究，并与正常人星形胶质细胞（NHA）的细胞毒性进行了比较。发现HL对A172的IC50值在2.68-0.95μM的范围内,而对LN229的IC50值在9.55-0.85μM的范围内。同样，化合物L对A172显示1.9-0.271μM和对LN229显示1.2-0.27μM的范围。与对照组相比，在用L处理的GBM细胞中观察到细胞周期停滞，根据细胞毒性和流式细胞术结果，提示L可能引发GBM细胞凋亡。还使用DPPH自由基研究了合成化合物的抗氧化活性。
