• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

新型苯并恶唑-苯甲酰胺化合物的设计、合成、分子模拟及生物评价：以 2-硫乙酰胺为连接基的潜在抗增殖剂、VEGFR-2 抑制剂和凋亡诱导剂。

Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

机构信息

Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

出版信息

J Enzyme Inhib Med Chem. 2022 Dec;37(1):1587-1599. doi: 10.1080/14756366.2022.2081844.

DOI:10.1080/14756366.2022.2081844
PMID:35637622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9176662/
Abstract

A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates - was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds , - and showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound. Furthermore, compounds and showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that and induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that and induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds and might serve as promising candidates for future anticancer therapy development.

摘要

设计了一系列新型的 2-硫代乙酰胺连接的苯并恶唑-苯甲酰胺缀合物，作为血管内皮生长因子受体-2（VEGFR-2）的潜在抑制剂。评估了所制备的化合物的潜在抗肿瘤活性，并使用正常人成纤维细胞（WI-38）细胞估计其相应的选择性细胞毒性。与用作参考化合物的索拉非尼相比，化合物 、 和 对 HCT-116 和 MCF-7 癌细胞系表现出良好的选择性和优异的细胞毒性活性。此外，化合物 和 表现出很强的 VEGFR-2 抑制活性。细胞周期进展分析表明， 和 诱导细胞周期在 G2/M 期停滞，同时前 G1 细胞群增加。进一步的药理研究表明， 和 在两种细胞系中诱导细胞凋亡并抑制抗凋亡 Bcl-2 和 Bcl-xL 蛋白的表达。因此，化合物 和 可能成为未来癌症治疗开发的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/a8de305289eb/IENZ_A_2081844_F0010_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/15b52fdbf1c8/IENZ_A_2081844_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/5be3983594d5/IENZ_A_2081844_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/1782c54a8fa1/IENZ_A_2081844_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/65b92a5d9f2f/IENZ_A_2081844_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/80a020dfdd75/IENZ_A_2081844_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/5f32a1e306c7/IENZ_A_2081844_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/7aab8ace4555/IENZ_A_2081844_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/7426f259ffc4/IENZ_A_2081844_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/cd18a818af0b/IENZ_A_2081844_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/ada4a17cd1e2/IENZ_A_2081844_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/261fb9ce1020/IENZ_A_2081844_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/a8de305289eb/IENZ_A_2081844_F0010_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/15b52fdbf1c8/IENZ_A_2081844_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/5be3983594d5/IENZ_A_2081844_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/1782c54a8fa1/IENZ_A_2081844_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/65b92a5d9f2f/IENZ_A_2081844_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/80a020dfdd75/IENZ_A_2081844_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/5f32a1e306c7/IENZ_A_2081844_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/7aab8ace4555/IENZ_A_2081844_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/7426f259ffc4/IENZ_A_2081844_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/cd18a818af0b/IENZ_A_2081844_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/ada4a17cd1e2/IENZ_A_2081844_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/261fb9ce1020/IENZ_A_2081844_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/9176662/a8de305289eb/IENZ_A_2081844_F0010_C.jpg

相似文献

1
Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.新型苯并恶唑-苯甲酰胺化合物的设计、合成、分子模拟及生物评价：以 2-硫乙酰胺为连接基的潜在抗增殖剂、VEGFR-2 抑制剂和凋亡诱导剂。
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1587-1599. doi: 10.1080/14756366.2022.2081844.
2
Design, synthesis, molecular docking, and anticancer activity of benzoxazole derivatives as VEGFR-2 inhibitors.苯并恶唑衍生物的设计、合成、分子对接及作为 VEGFR-2 抑制剂的抗癌活性。
Arch Pharm (Weinheim). 2019 Oct;352(10):e1900113. doi: 10.1002/ardp.201900113. Epub 2019 Aug 25.
3
Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation.基于苯并恶唑的 VEGFR-2 抑制剂和凋亡诱导剂的修饰：设计、合成与抗增殖活性评价。
Molecules. 2022 Aug 8;27(15):5047. doi: 10.3390/molecules27155047.
4
New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and studies.新型苯并恶唑衍生物作为潜在的 VEGFR-2 抑制剂和凋亡诱导剂：设计、合成、抗增殖评估、流式细胞分析和研究。
J Enzyme Inhib Med Chem. 2022 Dec;37(1):397-410. doi: 10.1080/14756366.2021.2015343.
5
Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, studies, and antiproliferative evaluation.苯并恶唑衍生物作为新型 VEGFR-2 抑制剂和凋亡诱导剂的设计、合成、研究及抗增殖活性评价
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2063-2077. doi: 10.1080/14756366.2022.2103552.
6
Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme.靶向VEGFR-2酶的新型三唑并[3,4-a]酞嗪衍生物的设计、合成、体外抗癌活性、ADMET特性及分子对接
Anticancer Agents Med Chem. 2018;18(8):1184-1196. doi: 10.2174/1871520618666180412123833.
7
EGFR/VEGFR-2 dual inhibitor and apoptotic inducer: Design, synthesis, anticancer activity and docking study of new 2-thioxoimidazolidin-4one derivatives.表皮生长因子受体/血管内皮生长因子受体-2 双重抑制剂和凋亡诱导剂：新型 2-硫代亚氨唑烷-4-酮衍生物的设计、合成、抗癌活性及对接研究。
Life Sci. 2021 Jul 15;277:119531. doi: 10.1016/j.lfs.2021.119531. Epub 2021 Apr 21.
8
Benzoxazole/benzothiazole-derived VEGFR-2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations.苯并恶唑/苯并噻唑衍生的 VEGFR-2 抑制剂：设计、合成、分子对接和抗癌评估。
Arch Pharm (Weinheim). 2019 Dec;352(12):e1900178. doi: 10.1002/ardp.201900178. Epub 2019 Oct 9.
9
Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis.合成、抗癌作用及新型噻唑基吡唑并香豆素衍生物的分子模拟，该衍生物针对 VEGFR-2 激酶并诱导细胞周期停滞和细胞凋亡。
Bioorg Chem. 2019 Apr;85:253-273. doi: 10.1016/j.bioorg.2018.12.040. Epub 2019 Jan 3.
10
Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine-2,4-dione derivatives as VEGFR-2 inhibitors.新型噻唑烷-2,4-二酮衍生物作为 VEGFR-2 抑制剂的设计、合成、对接、ADMET 分析和抗癌评估。
Arch Pharm (Weinheim). 2021 Jul;354(7):e2000491. doi: 10.1002/ardp.202000491. Epub 2021 Mar 31.

引用本文的文献

1
Design, synthesis, and cytotoxic evaluation of quinazoline-based derivatives as VEGER-2 inhibitors: comparative study against EGFR kinase activity, induction of apoptosis, and molecular docking study.基于喹唑啉的衍生物作为VEGER-2抑制剂的设计、合成及细胞毒性评价：针对EGFR激酶活性、细胞凋亡诱导及分子对接研究的比较性研究
RSC Adv. 2025 Aug 21;15(36):29593-29612. doi: 10.1039/d5ra03829d. eCollection 2025 Aug 18.
2
Novel -Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations.新型芳基甲基苯胺/查尔酮杂合体作为潜在的 VEGFR 抑制剂：合成、生物评价和分子动力学模拟。
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2278022. doi: 10.1080/14756366.2023.2278022. Epub 2023 Nov 20.
3

本文引用的文献

1
New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with docking, ADMET, toxicity, and DFT studies.新型基于喹喔啉的血管内皮生长因子受体-2（VEGFR-2）抑制剂：设计、合成以及通过对接、药物代谢动力学、毒性和密度泛函理论研究进行的抗增殖评估
RSC Adv. 2021 Oct 12;11(48):30315-30328. doi: 10.1039/d1ra05925d. eCollection 2021 Sep 6.
2
Structure-Activity Relationship Analysis of Benzimidazoles as Emerging Anti-Inflammatory Agents: An Overview.作为新型抗炎药物的苯并咪唑类化合物的构效关系分析：综述
Pharmaceuticals (Basel). 2021 Jul 11;14(7):663. doi: 10.3390/ph14070663.
3
Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers.
Synthesis, biological evaluation and computer-aided discovery of new thiazolidine-2,4-dione derivatives as potential antitumor VEGFR-2 inhibitors.新型噻唑烷-2,4-二酮衍生物作为潜在抗肿瘤VEGFR-2抑制剂的合成、生物学评价及计算机辅助发现
RSC Adv. 2023 Sep 19;13(40):27801-27827. doi: 10.1039/d3ra05689a. eCollection 2023 Sep 18.
4
Design, synthesis, studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.新型嘧啶-5-腈衍生物作为潜在抗增殖剂、VEGFR-2抑制剂和凋亡诱导剂的设计、合成、研究及生物学评价
RSC Adv. 2023 Jul 24;13(32):22122-22147. doi: 10.1039/d3ra04182d. eCollection 2023 Jul 19.
新型 3-甲基喹喔啉衍生物作为 VEGFR-2 抑制剂和凋亡诱导剂的设计、合成、对接、ADMET 研究和抗癌评估。
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1760-1782. doi: 10.1080/14756366.2021.1956488.
4
Synthesis of benzoxazole-based vorinostat analogs and their antiproliferative activity.苯并恶唑类伏立诺他类似物的合成及其抗增殖活性。
Bioorg Chem. 2021 Sep;114:105132. doi: 10.1016/j.bioorg.2021.105132. Epub 2021 Jun 28.
5
Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-:3',4'-]quinoxaline derivatives as anticancer agents and apoptosis inducers.基于双([1,2,4]三唑)[4,3-:3',4'-]喹喔啉衍生物的新型 VEGFR-2 抑制剂的发现及其作为抗癌和诱导细胞凋亡剂的作用。
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1093-1114. doi: 10.1080/14756366.2021.1915303.
6
Design, synthesis and evaluation of novel enzalutamide analogues as potential anticancer agents.新型恩杂鲁胺类似物作为潜在抗癌药物的设计、合成与评价
Heliyon. 2021 Mar 8;7(3):e06227. doi: 10.1016/j.heliyon.2021.e06227. eCollection 2021 Mar.
7
Synthesis, antimicrobial activity, density functional modelling and molecular docking with COVID-19 main protease studies of benzoxazole derivative: 2-(p-chloro-benzyl)-5-[3-(4-ethly-1-piperazynl) propionamido]-benzoxazole.苯并恶唑衍生物：2-(对氯苄基)-5-[3-(4-乙基-1-哌嗪基)丙酰胺基]-苯并恶唑的合成、抗菌活性、密度泛函建模及与新冠病毒主要蛋白酶的分子对接研究
J Mol Struct. 2021 Aug 5;1237:130413. doi: 10.1016/j.molstruc.2021.130413. Epub 2021 Apr 8.
8
New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis.新型喹喔啉衍生物作为具有抗癌和促凋亡活性的 VEGFR-2 抑制剂：设计、分子模拟和合成。
Bioorg Chem. 2021 May;110:104807. doi: 10.1016/j.bioorg.2021.104807. Epub 2021 Mar 5.
9
Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations.靛红-噻唑并[3,2-a]苯并咪唑杂合体的开发作为新型 CDK2 抑制剂，具有很强的体外凋亡抗增殖活性：合成、生物学和分子动力学研究。
Bioorg Chem. 2021 May;110:104748. doi: 10.1016/j.bioorg.2021.104748. Epub 2021 Feb 18.
10
Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent and Evaluation for CDK2 Inhibition Activity.一些新型苯并咪唑衍生物的合成及其作为抗癌剂和 CDK2 抑制活性的评价。
Med Chem. 2022;18(2):238-248. doi: 10.2174/1573406417666210304100830.