一类新型乙酰喹啉磺酰胺衍生物的合成、抗乳腺癌活性及分子对接研究

Krzysztof Marciniec, Bartosz Pawełczak, M. Latocha, L. Skrzypek, M. Maciążek-Jurczyk, S. Boryczka
{"title":"一类新型乙酰喹啉磺酰胺衍生物的合成、抗乳腺癌活性及分子对接研究","authors":"Krzysztof Marciniec, Bartosz Pawełczak, M. Latocha, L. Skrzypek, M. Maciążek-Jurczyk, S. Boryczka","doi":"10.3390/molecules22020300","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"17 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"15","resultStr":"{\"title\":\"Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives\",\"authors\":\"Krzysztof Marciniec, Bartosz Pawełczak, M. Latocha, L. Skrzypek, M. Maciążek-Jurczyk, S. Boryczka\",\"doi\":\"10.3390/molecules22020300\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":19033,\"journal\":{\"name\":\"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry\",\"volume\":\"17 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"15\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/molecules22020300\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/molecules22020300","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Single Laboratory Validation of a Quantitative Core Shell-Based LC Separation for the Evaluation of Silymarin Variability and Associated Antioxidant Activity of Pakistani Ecotypes of Milk Thistle (Silybum Marianum L.) Acknowledgement to Reviewers of Molecules in 2017 One-Bath Pretreatment for Enhanced Color Yield of Ink-Jet Prints Using Reactive Inks Prediction of Antimicrobial and Antioxidant Activities of Mexican Propolis by 1H-NMR Spectroscopy and Chemometrics Data Analysis Photophysics and Photochemistry of Canonical Nucleobases’ Thioanalogs: From Quantum Mechanical Studies to Time Resolved Experiments
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1