Krzysztof Marciniec, Bartosz Pawełczak, M. Latocha, L. Skrzypek, M. Maciążek-Jurczyk, S. Boryczka
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引用次数: 15
摘要
本研究设计、合成了一系列区域异构体乙酰氨基喹啉,并通过4-[3-(4-碘苯基)-2-(4-硝基苯基)- 2h -5-四氮唑]-1,3-苯二磺酸盐(WST-1)实验,在体外测试了它们对三种人乳腺癌细胞系(T47D, MCF-7和MDA-MB-231)和人正常成纤维细胞(HFF-1)的抗增殖活性。所测乙基喹啉磺胺类药物的抗增殖活性与顺铂相当。生物实验结果表明,大部分化合物具有较强的抗肿瘤活性,部分化合物对多种肿瘤细胞系的杀伤效果优于阳性对照顺铂。其中,4-(3-丙基硫代)-7-[n -甲基- n -(3-丙基)磺胺酰]喹啉对T47D细胞具有显著的抗增殖活性,IC50值为0.07µM。此外,2-(3-丙基硫代)-6-[n -甲基- n -(3-丙基)磺基]喹啉和2-(3-丙基硒基)-6-[n -甲基- n -(3-丙基)磺基]喹啉对MDA-MB-231细胞显示出高效的抗肿瘤活性,IC50值分别为0.09和0.50µM。此外,大多数被测化合物对正常HFF-1细胞系显示出微弱的细胞毒性作用。此外,为了提示其活性的作用机制,所有化合物都停靠在两种人类细胞色素P450 (CYP)同工酶的结合位点上。这些数据表明,一些标题化合物显示出显著的细胞毒活性,可能针对CYPs途径。
Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives
In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio)-7-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC50 values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[N-methyl-N-(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC50 values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP) isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways.