• 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

探究（E）-N'-亚苄基吡嗪-2-碳酰肼及其衍生物的抗分枝杆菌和抗增殖活性机制

Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives.

作者信息

Houngbedji Priam-Amedeo, Nawrot Daria Elżbieta, Janďourek Ondřej, Konečná Klára, Novák Martin, Paterová Pavla, Bárta Pavel, Rambaher Martina Hrast, Novotná Eva, Castellano Carlo, Mori Matteo, Meneghetti Fiorella, Záhorszká Monika, Korduláková Jana, Zitko Jan

机构信息

Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.

Biomedical Research Centre, University Hospital Hradec Králové, Sokolská 581, 500 05, Hradec Králové, Czech Republic.

出版信息

ChemMedChem. 2025 Sep 25;20(18):e202500085. doi: 10.1002/cmdc.202500085. Epub 2025 Aug 29.

DOI:10.1002/cmdc.202500085
PMID:40879650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12479386/
Abstract

A series of 33 (E)-N'-benzylidenepyrazine-2-carbohydrazides and their derivatives were synthesized and tested for biological activity. Benzylidene derivatives with 2-OH substitution on the phenyl ring (18: R = 2-OH, 21: R = 2,3-diOH, and 22: R = 2,4-diOH) exhibit various biological activities. Compounds 18 and 21 demonstrate antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. tuberculosis H37Rv, and M. aurum, with minimum inhibitory concentration values ranging from 15.625 to 62.5 μg mL. Compounds 18, 21, and 22 show mild cytotoxicity on several human cell lines (IC ranging from 70.2 to 500 μM). Crystallographic studies confirm the (E)-configuration of compound 18 and a nearly planar molecular conformation. Due to their structural similarity with salicylaldehyde isonicotinoyl hydrazone (SIH), a known iron chelator, selected compounds were tested for iron-chelating properties, revealing comparable or superior activity. Mechanistic assays targeting enoyl-[acyl carrier protein] reductase (InhA), isocitrate lyase (ICL), and lipid/mycolic acid biosynthesis show no significant inhibition, suggesting a nonspecific mechanism potentially linked to iron chelation. A correlation is observed between chelating activity and cytotoxicity, while antimycobacterial activity appears to involve additional mechanisms. Pharmacokinetic studies with compound 18 reveal no specific plasma metabolites, and no significant metabolites are detected after incubation with human liver microsomes.

摘要

合成了一系列33种（E）-N'-亚苄基吡嗪-2-碳酰肼及其衍生物，并对其进行了生物活性测试。在苯环上具有2-OH取代的亚苄基衍生物（18：R = 2-OH，21：R = 2,3-二OH，22：R = 2,4-二OH）表现出多种生物活性。化合物18和21对结核分枝杆菌H37Ra、结核分枝杆菌H37Rv和金色分枝杆菌具有抗分枝杆菌活性，最低抑菌浓度值范围为15.625至62.5μg/mL。化合物18、21和22对几种人类细胞系表现出轻度细胞毒性（IC范围为70.2至500μM）。晶体学研究证实了化合物18的（E）-构型和近乎平面的分子构象。由于它们与已知的铁螯合剂水杨醛异烟酰腙（SIH）结构相似，对所选化合物进行了铁螯合性能测试，结果显示出相当或更高的活性。针对烯酰-[酰基载体蛋白]还原酶（InhA）、异柠檬酸裂合酶（ICL）和脂质/分枝菌酸生物合成的机制分析显示无明显抑制作用，表明可能与铁螯合相关的非特异性机制。观察到螯合活性与细胞毒性之间存在相关性，而抗分枝杆菌活性似乎涉及其他机制。化合物18的药代动力学研究表明没有特定的血浆代谢物，与人肝微粒体孵育后未检测到明显的代谢物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/2df09ec0bc76/CMDC-20-e202500085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/eb23eb10542d/CMDC-20-e202500085-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/1f118593ca5d/CMDC-20-e202500085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/629142e215e7/CMDC-20-e202500085-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/9dfb2a95f65e/CMDC-20-e202500085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/52b6a7768ca3/CMDC-20-e202500085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/dad05dcc321c/CMDC-20-e202500085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/a55efd2486f3/CMDC-20-e202500085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/04aa9ade5583/CMDC-20-e202500085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/2df09ec0bc76/CMDC-20-e202500085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/eb23eb10542d/CMDC-20-e202500085-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/1f118593ca5d/CMDC-20-e202500085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/629142e215e7/CMDC-20-e202500085-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/9dfb2a95f65e/CMDC-20-e202500085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/52b6a7768ca3/CMDC-20-e202500085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/dad05dcc321c/CMDC-20-e202500085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/a55efd2486f3/CMDC-20-e202500085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/04aa9ade5583/CMDC-20-e202500085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0c/12479386/2df09ec0bc76/CMDC-20-e202500085-g008.jpg

相似文献

1
Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives.探究（E）-N'-亚苄基吡嗪-2-碳酰肼及其衍生物的抗分枝杆菌和抗增殖活性机制
ChemMedChem. 2025 Sep 25;20(18):e202500085. doi: 10.1002/cmdc.202500085. Epub 2025 Aug 29.
2
Isoniazid-Derived Hydrazones Featuring Piperazine/Piperidine Rings: Design, Synthesis, and Investigation of Antitubercular Activity.具有哌嗪/哌啶环的异烟肼衍生腙：抗结核活性的设计、合成与研究
Biomolecules. 2025 Sep 11;15(9):1305. doi: 10.3390/biom15091305.
3
Promising Antimycobacterial Agents: Salicylidenehydrazines.有前景的抗分枝杆菌药物：水杨醛肼类化合物。
Arch Pharm (Weinheim). 2025 Jul;358(7):e70065. doi: 10.1002/ardp.70065.
4
Hybrid virtual screening identifies dipyrazole carboxamide derivatives as novel direct InhA inhibitors with antitubercular activity.混合虚拟筛选鉴定出二吡唑甲酰胺衍生物为具有抗结核活性的新型直接InhA抑制剂。
Biochim Biophys Acta Gen Subj. 2025 Jul;1869(8):130827. doi: 10.1016/j.bbagen.2025.130827. Epub 2025 May 26.
5
Synthesis and antimycobacterial evaluation of N'-(E)-heteroaromaticpyrazine-2-carbohydrazide derivatives.N'-(E)-杂环吡嗪-2-甲酰肼衍生物的合成及抗分枝杆菌活性评价。
Med Chem. 2011 May;7(3):245-9. doi: 10.2174/157340611795564303.
6
Noncovalent inhibitors of DprE1 for tuberculosis treatment: design, synthesis, characterization, and studies of 4-oxo-1,4-dihydroquinazolinylpyrazine-2-carboxamides.用于结核病治疗的DprE1非共价抑制剂：4-氧代-1,4-二氢喹唑啉基吡嗪-2-甲酰胺的设计、合成、表征及研究
J Biomol Struct Dyn. 2024 Nov 15:1-15. doi: 10.1080/07391102.2024.2427368.
7
From Bench to Bioactivity: Pyranopyrazole Synthesis, Anticancer, Antimicrobial Efficacy, DFT, Molecular Docking, and Molecular Dynamic Insights.从实验台到生物活性：吡喃并吡唑的合成、抗癌、抗菌功效、密度泛函理论、分子对接及分子动力学见解
Anticancer Agents Med Chem. 2025;25(16):1253-1271. doi: 10.2174/0118715206376210250319053528.
8
Exploring the Anti-Tubercular Potential of 2-(1H-Pyrazol-1-yl) Pyrimidine: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.探索2-(1H-吡唑-1-基)嘧啶的抗结核潜力：设计、合成、生物学评价及分子对接研究
Chem Biodivers. 2025 Jul;22(7):e202500321. doi: 10.1002/cbdv.202500321. Epub 2025 Mar 29.
9
3,5-disubstituted pyridines with potent activity against drug-resistant clinical isolates.对耐药临床分离株具有强效活性的3,5-二取代吡啶。
Future Med Chem. 2024;16(22):2351-2369. doi: 10.1080/17568919.2024.2403963. Epub 2024 Oct 3.
10
Investigation of novel nimesulide derivatives against breast cancer.新型尼美舒利衍生物抗乳腺癌的研究
Bioorg Chem. 2025 Aug 6;164:108850. doi: 10.1016/j.bioorg.2025.108850.

本文引用的文献

1
Antimycobacterial pyridine carboxamides: From design to in vivo activity.抗分枝杆菌吡啶甲酰胺类药物：从设计到体内活性。
Eur J Med Chem. 2023 Oct 5;258:115617. doi: 10.1016/j.ejmech.2023.115617. Epub 2023 Jun 30.
2
[Treatment of tuberculosis: what is new?].[结核病的治疗：有哪些新进展？]
Inn Med (Heidelb). 2023 Jul;64(7):701-707. doi: 10.1007/s00108-023-01523-z. Epub 2023 Jun 14.
3
Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets.结核病：发病机制、现行治疗方案及新药靶点。
Int J Mol Sci. 2023 Mar 8;24(6):5202. doi: 10.3390/ijms24065202.
4
Hybridization Approach Toward Novel Antituberculars: Design, Synthesis, and Biological Evaluation of Compounds Combining Pyrazinamide and 4-Aminosalicylic Acid.杂交方法研究新型抗结核药物：结合吡嗪酰胺和 4-氨基水杨酸的化合物的设计、合成和生物学评价。
ACS Infect Dis. 2023 Jan 13;9(1):79-96. doi: 10.1021/acsinfecdis.2c00433. Epub 2022 Dec 28.
5
Lessons Learnt and the Way Forward for Drug Development Against Isocitrate Lyase from .异柠檬酸裂解酶药物开发的经验教训和未来方向
Protein Pept Lett. 2022;29(12):1031-1041. doi: 10.2174/0929866529666221006121831.
6
Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase.取代的 N-苯基马来酰胺作为分枝杆菌和分枝杆菌异柠檬酸裂解酶的抑制剂。
Eur J Pharm Sci. 2022 Sep 1;176:106252. doi: 10.1016/j.ejps.2022.106252. Epub 2022 Jul 3.
7
Iron chelators in cancer therapy.癌症治疗中的铁螯合剂。
Biometals. 2020 Oct;33(4-5):201-215. doi: 10.1007/s10534-020-00243-3. Epub 2020 Aug 5.
8
The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD.结核分枝杆菌泛二氢蝶酸合成酶的吡嗪酰胺作用的分子基础
Nat Commun. 2020 Jan 17;11(1):339. doi: 10.1038/s41467-019-14238-3.
9
New Insights into the Mechanism of Action of the Thienopyrimidine Antitubercular Prodrug TP053.新型噻吩嘧啶类抗结核前药 TP053 作用机制的新见解。
ACS Infect Dis. 2020 Feb 14;6(2):313-323. doi: 10.1021/acsinfecdis.9b00388. Epub 2019 Dec 2.
10
Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and Their Trifluoromethyl Analogues as Highly Efficient Antitubercular Agents Inhibiting Decaprenylphosphoryl-β-d-ribofuranose 2'-Oxidase.含 3,5-二硝基苯基的 1,2,4-三唑类和其三氟甲基类似物的开发作为高效抗结核剂抑制鲨烯磷酸化-β-d-核糖呋喃糖 2'-氧化酶。
J Med Chem. 2019 Sep 12;62(17):8115-8139. doi: 10.1021/acs.jmedchem.9b00912. Epub 2019 Aug 22.