Suppr超能文献

基于呋喃和呋喃嘧啶的衍生物：合成、VEGFR-2抑制及细胞毒性

Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and Cytotoxicity.

作者信息

Abd El-Haleem Akram H, Kassem Manar Abd El-Karim, Elnagar Mohamed R, Abbas Safinaz E-S, El Kerdawy Ahmed M, Farouk Ahmed K B A W

机构信息

Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Sixth of October City, Giza 77, Egypt.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11823, Egypt.

出版信息

ACS Med Chem Lett. 2024 Nov 25;15(12):2150-2157. doi: 10.1021/acsmedchemlett.4c00438. eCollection 2024 Dec 12.

DOI:10.1021/acsmedchemlett.4c00438
PMID:39691520
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11647721/
Abstract

New derivatives -, , -, -, , , , -, -, and were synthesized and evaluated for their VEGFR-2 inhibition. Compounds , , and showed remarkable enzyme inhibition IC = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 cancer cell lines in addition to WI-38. Compound displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC = 6.66 and 8.51 μM) compared to sorafenib (IC = 6.60 and 8.78 μM). Cell cycle analysis and apoptotic assay of in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of apoptosis. Western blot analysis of compound revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of showed inhibition of wound closure. Additionally, molecular modeling studies of compounds , , and were carried out.

摘要

合成了新的衍生物-、-、-、-、、、、-、-和，并对其VEGFR-2抑制活性进行了评估。相对于索拉非尼（IC = 41.1 nM），化合物、和表现出显著的酶抑制作用（IC分别为57.1、42.5和52.5 nM），并除了在WI-38细胞系中测试外，还对其针对HepG2、MCF-7、A549、HT-29和PC3癌细胞系的细胞毒性进行了评估。与索拉非尼（IC分别为6.60和8.78 μM）相比，化合物对A549和HT-29表现出几乎等效的细胞毒性（IC分别为6.66和8.51 μM）。对HT-29细胞系中的进行细胞周期分析和凋亡检测，结果显示除诱导凋亡外，细胞生长停滞于G2/M期。对化合物进行蛋白质免疫印迹分析显示VEGFR-2失活。此外，对进行伤口愈合检测显示伤口闭合受到抑制。另外，还对化合物、和进行了分子模拟研究。

相似文献

1
Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and Cytotoxicity.基于呋喃和呋喃嘧啶的衍生物：合成、VEGFR-2抑制及细胞毒性
ACS Med Chem Lett. 2024 Nov 25;15(12):2150-2157. doi: 10.1021/acsmedchemlett.4c00438. eCollection 2024 Dec 12.
2
Development of New Thiadiazole Derivatives as VEGFR-2 Inhibitors With Anticancer and Proapoptotic Activities‏.新型噻二唑衍生物作为具有抗癌和促凋亡活性的VEGFR-2抑制剂的研发
Arch Pharm (Weinheim). 2025 Jul;358(7):e70042. doi: 10.1002/ardp.70042.
3
Design, synthesis, and biological evaluation of pyrazole-based combretastatin A-4 analogues as potential cytotoxic agents.基于吡唑的康普他汀A-4类似物作为潜在细胞毒性剂的设计、合成及生物学评价
Bioorg Chem. 2025 Jun 16;163:108691. doi: 10.1016/j.bioorg.2025.108691.
4
New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies.新型噻唑烷-4-酮类化合物作为靶向表皮生长因子受体的抗宫颈癌药物：设计、合成及计算研究
Future Med Chem. 2025 Jan;17(1):75-91. doi: 10.1080/17568919.2024.2437976. Epub 2024 Dec 9.
5
Triazole-functionalized benzofuran and benzothiophene semicarbazides as novel VEGFR-2-targeted anti-cancer agents.作为新型VEGFR-2靶向抗癌剂的三唑官能化苯并呋喃和苯并噻吩氨基脲
Bioorg Chem. 2025 Aug;163:108702. doi: 10.1016/j.bioorg.2025.108702. Epub 2025 Jun 22.
6
Anticancer Potential of Halogen Derivatives of Methyl 6-Acetyl-5-Hydroxy-2-Methyl-1-Benzofuran-3-Carboxylate.6-乙酰基-5-羟基-2-甲基-1-苯并呋喃-3-羧酸甲酯的卤素衍生物的抗癌潜力
Int J Mol Sci. 2025 Jun 8;26(12):5493. doi: 10.3390/ijms26125493.
7
Novel pyrazole carboxylate derivatives as lonazolac bioisosteres with selective COX-2 inhibition: design, synthesis and anti-inflammatory activity.新型吡唑羧酸酯衍生物作为洛那唑酸生物电子等排体具有选择性COX-2抑制作用：设计、合成及抗炎活性
Mol Divers. 2025 May 22. doi: 10.1007/s11030-025-11220-8.
8
Synthesis and apoptotic induction of sulfonamide-based chalcone hybrids as first-in-class dual histone deacetylase‑carbonic anhydrase inhibitors with potential anti-tubulin activity.基于磺胺的查耳酮杂化物的合成及其凋亡诱导作用，作为具有潜在抗微管蛋白活性的一流双组蛋白脱乙酰酶-碳酸酐酶抑制剂。
Bioorg Chem. 2025 Jun 20;163:108694. doi: 10.1016/j.bioorg.2025.108694.
9
Synthesis, antiproliferative evaluation and studies of new quinazoline derivatives as VEGFR-2 inhibitors.新型喹唑啉衍生物作为VEGFR-2抑制剂的合成、抗增殖活性评价及研究
Future Med Chem. 2025 Jun;17(12):1407-1422. doi: 10.1080/17568919.2025.2525073. Epub 2025 Jul 4.
10
Mitochondrial-targeted iridium(III) complexes suppress tumor growth through inducting immunogenic cell death to activate immune response.线粒体靶向铱（III）配合物通过诱导免疫原性细胞死亡来激活免疫反应，从而抑制肿瘤生长。
Eur J Med Chem. 2025 Nov 5;297:117926. doi: 10.1016/j.ejmech.2025.117926. Epub 2025 Jul 1.

引用本文的文献

1
Metal-Free Catalytic Synthesis of Tetrasubstituted Furans from -Hydroxy Ketones and Cyano Compounds.由α-羟基酮和氰基化合物无金属催化合成四取代呋喃
Molecules. 2025 Apr 19;30(8):1832. doi: 10.3390/molecules30081832.

本文引用的文献

1
An assessment of EGFR and HER2 inhibitors with structure activity relationship of fused pyrimidine derivatives for breast cancer: a brief review.评估 EGFR 和 HER2 抑制剂与融合嘧啶衍生物的结构活性关系在乳腺癌中的应用：简要综述。
J Biomol Struct Dyn. 2024 Feb-Mar;42(3):1564-1581. doi: 10.1080/07391102.2023.2204351. Epub 2023 May 9.
2
Synthesis and study of pyrimidine-phthalimide hybrids as VEGFR2 inhibitors with antiproliferative activity.嘧啶-邻苯二甲酰亚胺杂化物作为具有抗增殖活性的VEGFR2抑制剂的合成与研究
Future Med Chem. 2023 Apr;15(8):661-677. doi: 10.4155/fmc-2023-0025. Epub 2023 Apr 26.
3
The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF.VEGF 在肿瘤诱导血管生成中的作用及 VEGF 靶向药物的研究进展。
Eur J Pharmacol. 2023 Jun 15;949:175586. doi: 10.1016/j.ejphar.2023.175586. Epub 2023 Mar 9.
4
Design and synthesis of some new 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines as multi tyrosine kinase inhibitors.设计并合成了一些新型 6-溴-2-(吡啶-3-基)-4-取代喹唑啉类化合物作为多靶点酪氨酸激酶抑制剂。
Bioorg Chem. 2022 Nov;128:106099. doi: 10.1016/j.bioorg.2022.106099. Epub 2022 Aug 17.
5
Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists.含磺酰基硫脲基团的噻唑烷-2,4-二酮类化合物作为有效的血管内皮生长因子受体-2（VEGFR-2）抑制剂和过氧化物酶体增殖物激活受体γ（PPARγ）激动剂的设计、分子对接、合成、抗癌及抗高血糖活性评估
Pharmaceuticals (Basel). 2022 Feb 14;15(2):226. doi: 10.3390/ph15020226.
6
Design and synthesis of novel furan, furo[2,3-d]pyrimidine and furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as potential VEGFR-2 inhibitors.设计和合成新型呋喃、呋[2,3-d]嘧啶和呋[3,2-e][1,2,4]三唑并[1,5-c]嘧啶衍生物作为潜在的 VEGFR-2 抑制剂。
Bioorg Chem. 2021 Nov;116:105336. doi: 10.1016/j.bioorg.2021.105336. Epub 2021 Sep 13.
7
Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives.血管生成素抑制剂对 VEGFR-2、PDGFR 和 FGFR 的抑制作用及对肺癌细胞生长的抑制作用：新型杂氮杂环香豆素衍生物的设计、合成、生物评价及分子对接。
Bioorg Med Chem Lett. 2021 Sep 15;48:128258. doi: 10.1016/j.bmcl.2021.128258. Epub 2021 Jul 9.
8
Synthesis and vasodilator activity of some pyridazin-3(2)-one based compounds.合成及部分哒嗪-3(2H)-酮类化合物的血管舒张活性。
Future Med Chem. 2020 Jan;12(1):37-50. doi: 10.4155/fmc-2019-0160. Epub 2019 Nov 11.
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
Type IIA - Type IIB protein tyrosine kinase inhibitors hybridization as an efficient approach for potent multikinase inhibitor development: Design, synthesis, anti-proliferative activity, multikinase inhibitory activity and molecular modeling of novel indolinone-based ureides and amides.IIA 型-IIB 型蛋白酪氨酸激酶抑制剂杂交作为一种有效的方法来开发有效的多激酶抑制剂：新型基于吲哚啉酮的脲和酰胺的设计、合成、抗增殖活性、多激酶抑制活性和分子模拟。
Eur J Med Chem. 2019 Feb 1;163:37-53. doi: 10.1016/j.ejmech.2018.11.061. Epub 2018 Nov 24.

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