Interaction of an anticancer oxygenated propenylbenzene derivatives with human topoisomerase II α and actin: molecular modeling and isothermal titration calorimetry studies

IF 3 3区 工程技术 Q2 CHEMISTRY, ANALYTICAL Journal of Thermal Analysis and Calorimetry Pub Date : 2024-09-02 DOI:10.1007/s10973-024-13569-8
Joanna Grzelczyk, Horacio Pérez-Sánchez, Jochem Nelen, Miguel Carmena-Bargueño, Ilona Gałązka-Czarnecka, Grażyna Budryn, Dawid Hernik, Elisabetta Brenna, Filip Boratyński
{"title":"Interaction of an anticancer oxygenated propenylbenzene derivatives with human topoisomerase II α and actin: molecular modeling and isothermal titration calorimetry studies","authors":"Joanna Grzelczyk, Horacio Pérez-Sánchez, Jochem Nelen, Miguel Carmena-Bargueño, Ilona Gałązka-Czarnecka, Grażyna Budryn, Dawid Hernik, Elisabetta Brenna, Filip Boratyński","doi":"10.1007/s10973-024-13569-8","DOIUrl":null,"url":null,"abstract":"<p>Cancer diseases are one of the most common causes of death. It is important to reduce the proliferation of cancer cells at an early stage, but also to limit their migration. There is a need to find new compounds of moderate anticancer prevention activity for long administration. TOPIIα and actin are proteins that in states of inflammation can cause the progression of cancer and neoblastic cell migrations. Looking for compounds that will work comprehensively in preventing cancer, interacting with both TOPIIα and actin is crucial/was our aim. In this study, the antioxidant properties of propenylbenzene derivatives and their affinity to bind actin and TOPIIα causing inhibition of their functions were evaluated. The ligand–protein binding assay was carried out by isometric titration calorimetry (ITC), and molecular docking, and the antioxidant potential. The highest chelation activity was shown by 5b: 83.95% (FRAP 18.39 μmol Fe(II) mL<sup>−1</sup>). High affinity for actin and TOPIIα using ITC and docking was shown by diol forms. For actin the best ligands were 2b (∆H − 51.49 kJ mol<sup>−1</sup>, ∆G − 27.37 kJ mol<sup>−1</sup>) and 5b (∆H − 17.25 kJ mol<sup>−1</sup>, ∆G − 26.20 kJ mol<sup>−1</sup>), whereas for TOPIIα: 3b (∆H − 163.86 kJ mol<sup>−1</sup>, ∆G − 34.60 kJ mol<sup>−1</sup>) and 5b (∆H − 160.93 kJ mol<sup>−1</sup>, ∆G − 32.92 kJ mol<sup>−1</sup>). To confirm the occurrence of the interactions at the active site of the proteins, molecular docking and subsequent molecular dynamics simulations were performed, which showed for both actin and TOPIIα the highest enthalpy of interactions of 5b: − 34.94 kJ mol<sup>−1</sup> and − 25.52 kJ mol<sup>−1</sup>, respectively.</p>","PeriodicalId":678,"journal":{"name":"Journal of Thermal Analysis and Calorimetry","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thermal Analysis and Calorimetry","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s10973-024-13569-8","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0

Abstract

Cancer diseases are one of the most common causes of death. It is important to reduce the proliferation of cancer cells at an early stage, but also to limit their migration. There is a need to find new compounds of moderate anticancer prevention activity for long administration. TOPIIα and actin are proteins that in states of inflammation can cause the progression of cancer and neoblastic cell migrations. Looking for compounds that will work comprehensively in preventing cancer, interacting with both TOPIIα and actin is crucial/was our aim. In this study, the antioxidant properties of propenylbenzene derivatives and their affinity to bind actin and TOPIIα causing inhibition of their functions were evaluated. The ligand–protein binding assay was carried out by isometric titration calorimetry (ITC), and molecular docking, and the antioxidant potential. The highest chelation activity was shown by 5b: 83.95% (FRAP 18.39 μmol Fe(II) mL−1). High affinity for actin and TOPIIα using ITC and docking was shown by diol forms. For actin the best ligands were 2b (∆H − 51.49 kJ mol−1, ∆G − 27.37 kJ mol−1) and 5b (∆H − 17.25 kJ mol−1, ∆G − 26.20 kJ mol−1), whereas for TOPIIα: 3b (∆H − 163.86 kJ mol−1, ∆G − 34.60 kJ mol−1) and 5b (∆H − 160.93 kJ mol−1, ∆G − 32.92 kJ mol−1). To confirm the occurrence of the interactions at the active site of the proteins, molecular docking and subsequent molecular dynamics simulations were performed, which showed for both actin and TOPIIα the highest enthalpy of interactions of 5b: − 34.94 kJ mol−1 and − 25.52 kJ mol−1, respectively.

Abstract Image

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
抗癌含氧丙烯苯衍生物与人类拓扑异构酶 II α 和肌动蛋白的相互作用:分子建模和等温滴定量热研究
癌症是最常见的死亡原因之一。必须在早期阶段减少癌细胞的增殖,同时限制其迁移。因此,有必要寻找具有适度抗癌活性、可长期服用的新化合物。TOPIIα和肌动蛋白是一种蛋白质,在炎症状态下可导致癌症进展和新生细胞迁移。我们的目标是寻找能与 TOPIIα 和肌动蛋白相互作用的综合防癌化合物。本研究评估了丙烯基苯衍生物的抗氧化性及其与肌动蛋白和 TOPIIα 结合的亲和力,从而抑制它们的功能。通过等压滴定量热法(ITC)和分子对接法进行了配体与蛋白质的结合试验,并评估了抗氧化潜力。5b 的螯合活性最高:83.95%(FRAP 18.39 μmol Fe(II) mL-1)。利用 ITC 和对接技术,二元醇形式显示出与肌动蛋白和 TOPIIα 的高亲和力。对于肌动蛋白,最佳配体是 2b (∆H - 51.49 kJ mol-1,∆G - 27.37 kJ mol-1)和 5b(∆H - 17.25 kJ mol-1,∆G - 26.20 kJ mol-1),而对于 TOPIIα:3b(∆H - 163.86 kJ mol-1,∆G - 34.60 kJ mol-1)和 5b(∆H - 160.93 kJ mol-1,∆G - 32.92 kJ mol-1)。为了证实在蛋白质的活性位点发生了相互作用,进行了分子对接和随后的分子动力学模拟,结果表明对于肌动蛋白和 TOPIIα 而言,5b 的相互作用焓最高,分别为 34.94 kJ mol-1 和 32.92 kJ mol-1:- 分别为 34.94 kJ mol-1 和 - 25.52 kJ mol-1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
8.50
自引率
9.10%
发文量
577
审稿时长
3.8 months
期刊介绍: Journal of Thermal Analysis and Calorimetry is a fully peer reviewed journal publishing high quality papers covering all aspects of thermal analysis, calorimetry, and experimental thermodynamics. The journal publishes regular and special issues in twelve issues every year. The following types of papers are published: Original Research Papers, Short Communications, Reviews, Modern Instruments, Events and Book reviews. The subjects covered are: thermogravimetry, derivative thermogravimetry, differential thermal analysis, thermodilatometry, differential scanning calorimetry of all types, non-scanning calorimetry of all types, thermometry, evolved gas analysis, thermomechanical analysis, emanation thermal analysis, thermal conductivity, multiple techniques, and miscellaneous thermal methods (including the combination of the thermal method with various instrumental techniques), theory and instrumentation for thermal analysis and calorimetry.
期刊最新文献
Thermal characterization of plat heat exchanger made from polymer biocomposite reinforced by silicon carbide Recent advances in thermal analysis and calorimetry presented at the 3rd Journal of Thermal Analysis and Calorimetry Conference and 9th V4 (Joint Czech–Hungarian–Polish–Slovakian) Thermoanalytical Conference (2023) Spalling behavior of high-strength polypropylene fiber-reinforced concrete subjected to elevated temperature Study of thermal behavior and crystallization kinetics of glass microspheres in the Y3Al5O12-Al2O3 system Size fraction characterisation of highly-calcareous and siliceous fly ashes
×
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