• 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

泛酸合成酶抑制剂——药物化学家的视角

Inhibitors of pantothenate synthetase of - a medicinal chemist perspective.

作者信息

Suresh Amaroju, Srinivasarao Singireddi, Khetmalis Yogesh Mahadu, Nizalapur Shashidhar, Sankaranarayanan Murugesan, Gowri Chandra Sekhar Kondapalli Venkata

机构信息

Department of Chemistry, Birla Institute of Technology & Science-Pilani Hyderabad Campus, Medchal District Hyderabad-500078 Telangana India

School of Chemistry, UNSW, Australia Sydney NSW 2052 Australia.

出版信息

RSC Adv. 2020 Oct 7;10(61):37098-37115. doi: 10.1039/d0ra07398a.

DOI:10.1039/d0ra07398a
PMID:35521286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9057165/
Abstract

Tuberculosis (TB), one of the most prevalent infections, is on the rise today. Although there are drugs available in the market to combat this lethal disorder, there are several shortcomings with the current drug regimen, such as prolonged treatment period, drug resistance, high cost, Hence, it is inevitable for the current researchers across the globe to embark on new strategies for TB drug discovery, which will yield highly active low cost drugs with a shorter treatment period. To achieve this, novel strategies need to be adopted to discover new drugs. Pantothenate Synthetase (PS) is one such striking drug target in (MTB). It was observed that the pantothenate biosynthetic pathway is crucial for the pathogenicity of MTB. Pantothenate is absent in mammals and needs to be obtained from dietary sources. Hence, the pantothenate biosynthesis pathway is an impending target for emerging new therapeutics to treat TB. Worldwide, several approaches have been implemented by researchers in the quest for these inhibitors such as high-throughput screening, simulating the reaction intermediate pantoyl adenylate, use of vibrant combinatorial chemistry, hybridization approach, virtual screening of databases, inhibitors based on the crystal structure of MTB PS, The present review recapitulates current developments in PS inhibitors, important analogues of numerous metabolic intermediates, and newly established inhibitors with innumerable chemical structures.

摘要

结核病(TB)是最常见的感染性疾病之一,如今其发病率正在上升。尽管市场上有药物可用于对抗这种致命疾病,但目前的药物治疗方案存在一些缺点,如治疗周期长、耐药性、成本高。因此,全球目前的研究人员不可避免地要着手探索结核病药物研发的新策略,以开发出治疗周期短、活性高且成本低的药物。要实现这一目标,需要采用新的策略来发现新药。泛酸合成酶(PS)就是结核分枝杆菌(MTB)中这样一个引人注目的药物靶点。据观察,泛酸生物合成途径对MTB的致病性至关重要。哺乳动物体内不存在泛酸,需要从饮食中获取。因此,泛酸生物合成途径是新兴的结核病治疗新疗法的一个迫切目标。在全球范围内,研究人员为寻找这些抑制剂采用了多种方法,如高通量筛选、模拟反应中间体泛酰腺苷酸、运用活跃的组合化学、杂交方法、数据库虚拟筛选、基于MTB PS晶体结构的抑制剂等。本综述概述了PS抑制剂的当前进展、众多代谢中间体的重要类似物以及具有无数化学结构的新发现抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/6049f347513d/d0ra07398a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/e5b0782665ef/d0ra07398a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/23bdc0c57f92/d0ra07398a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/7cdb23e02b14/d0ra07398a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/6049f347513d/d0ra07398a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/e5b0782665ef/d0ra07398a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/23bdc0c57f92/d0ra07398a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/7cdb23e02b14/d0ra07398a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7e/9057165/6049f347513d/d0ra07398a-f4.jpg

相似文献

1
Inhibitors of pantothenate synthetase of - a medicinal chemist perspective.泛酸合成酶抑制剂——药物化学家的视角
RSC Adv. 2020 Oct 7;10(61):37098-37115. doi: 10.1039/d0ra07398a.
2
Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase.反应中间体类似物作为泛酸合成酶的双底物抑制剂
Bioorg Med Chem. 2014 Mar 1;22(5):1726-35. doi: 10.1016/j.bmc.2014.01.017. Epub 2014 Jan 23.
3
Editorial: Current status and perspective on drug targets in tubercle bacilli and drug design of antituberculous agents based on structure-activity relationship.社论:结核杆菌药物靶点的现状与展望以及基于构效关系的抗结核药物设计
Curr Pharm Des. 2014;20(27):4305-6. doi: 10.2174/1381612819666131118203915.
4
Design of Novel Mycobacterium tuberculosis Pantothenate Synthetase Inhibitors: Virtual Screening, Synthesis and In Vitro Biological Activities.新型结核分枝杆菌泛酸合成酶抑制剂的设计:虚拟筛选、合成及体外生物学活性
Mol Inform. 2015 Feb;34(2-3):147-59. doi: 10.1002/minf.201400120. Epub 2015 Feb 17.
5
Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate.结核分枝杆菌泛酸合成酶的晶体结构及其与底物和反应中间体的复合物
Protein Sci. 2003 May;12(5):1097-108. doi: 10.1110/ps.0241803.
6
[Development of antituberculous drugs: current status and future prospects].[抗结核药物的研发:现状与未来前景]
Kekkaku. 2006 Dec;81(12):753-74.
7
Unearthing phytochemicals as natural inhibitors for pantothenate synthetase in : A computational approach.挖掘植物化学物质作为泛酸合成酶的天然抑制剂:一种计算方法。
Front Pharmacol. 2024 Jul 29;15:1403900. doi: 10.3389/fphar.2024.1403900. eCollection 2024.
8
Lead identification against using highly enriched active molecules against pantothenate synthetase.针对泛酸合成酶使用高度富集的活性分子进行先导化合物鉴定。
J Biomol Struct Dyn. 2024;42(20):11080-11097. doi: 10.1080/07391102.2023.2260483. Epub 2023 Sep 25.
9
Active site residues in Mycobacterium tuberculosis pantothenate synthetase required in the formation and stabilization of the adenylate intermediate.结核分枝杆菌泛酸合成酶中形成和稳定腺苷酸中间体所需的活性位点残基。
Biochemistry. 2004 Jun 8;43(22):7171-8. doi: 10.1021/bi049676n.
10
Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action.结核分枝杆菌泛酸合成酶的晶体结构,该酶作用过程的瞬间影像。
Biochemistry. 2006 Feb 14;45(6):1554-61. doi: 10.1021/bi051873e.

引用本文的文献

1
Harnessing subtractive genomics for drug target identification in Streptococcus agalactiae serotype v (atcc baa-611 / 2603 v/r) strain: An in-silico approach.利用消减基因组学鉴定无乳链球菌血清型V(ATCC BAA-611 / 2603 V/R)菌株中的药物靶点:一种计算机模拟方法。
PLoS One. 2025 Aug 21;20(8):e0319368. doi: 10.1371/journal.pone.0319368. eCollection 2025.
2
Review of Recent Advances in Thiazolidin-4-One Derivatives as Promising Antitubercular Agents (2021-Present).噻唑烷-4-酮衍生物作为有前景的抗结核药物的最新进展综述(2021年至今)
Molecules. 2025 May 17;30(10):2201. doi: 10.3390/molecules30102201.
3
Ajoene: a natural compound with enhanced antimycobacterial and antibiofilm properties mediated by efflux pump modulation and ROS generation against M. Smegmatis.

本文引用的文献

1
Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies.新型吡嗪类抗结核药物的设计、合成、生物评价及计算机模拟研究。
Bioorg Chem. 2020 Mar;96:103610. doi: 10.1016/j.bioorg.2020.103610. Epub 2020 Jan 25.
2
Harnessing Biological Insight to Accelerate Tuberculosis Drug Discovery.利用生物学洞察力加速结核病药物发现。
Acc Chem Res. 2019 Aug 20;52(8):2340-2348. doi: 10.1021/acs.accounts.9b00275. Epub 2019 Jul 30.
3
High throughput screening against pantothenate synthetase identifies amide inhibitors against and .
大蒜素:一种天然化合物,通过调节外排泵和产生 ROS 增强抗分枝杆菌和抗生物膜特性,对耻垢分枝杆菌有效。
Arch Microbiol. 2024 Nov 2;206(12):453. doi: 10.1007/s00203-024-04189-9.
4
Exploring Indonesian actinomycete extracts for anti-tubercular compounds: Integrating inhibition assessment, genomic analysis, and prediction of its target by molecular docking.探索印度尼西亚放线菌提取物中的抗结核化合物:整合抑制评估、基因组分析以及通过分子对接预测其靶点
Heliyon. 2024 Aug 4;10(15):e35648. doi: 10.1016/j.heliyon.2024.e35648. eCollection 2024 Aug 15.
5
Unearthing phytochemicals as natural inhibitors for pantothenate synthetase in : A computational approach.挖掘植物化学物质作为泛酸合成酶的天然抑制剂:一种计算方法。
Front Pharmacol. 2024 Jul 29;15:1403900. doi: 10.3389/fphar.2024.1403900. eCollection 2024.
6
Exploring optimal drug targets through subtractive proteomics analysis and pangenomic insights for tailored drug design in tuberculosis.通过消减蛋白质组学分析和泛基因组见解探索最佳药物靶点,以进行结核病的靶向药物设计。
Sci Rep. 2024 May 13;14(1):10904. doi: 10.1038/s41598-024-61752-6.
7
Expanding FTMap for Fragment-Based Identification of Pharmacophore Regions in Ligand Binding Sites.扩展 FTMap 以基于片段的方法鉴定配体结合位点中的药效基团区域。
J Chem Inf Model. 2024 Mar 25;64(6):2084-2100. doi: 10.1021/acs.jcim.3c01969. Epub 2024 Mar 8.
8
: Pathogenesis and therapeutic targets.发病机制与治疗靶点。
MedComm (2020). 2023 Sep 4;4(5):e353. doi: 10.1002/mco2.353. eCollection 2023 Oct.
9
Identification of the Seaweed Metabolites as Potential Anti-tubercular Agents Against Human Pantothenate synthetase: An In Silico Approach.从海藻代谢产物中鉴定潜在的抗结核药物靶点:一种基于计算机的方法。
Curr Microbiol. 2023 Aug 14;80(10):318. doi: 10.1007/s00284-023-03422-w.
10
In Silico Subtractive Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against Strain D39.基于计算机的减法蛋白质组学和分子对接方法用于鉴定针对D39菌株的新型抑制剂
Life (Basel). 2023 May 4;13(5):1128. doi: 10.3390/life13051128.
针对泛酸合成酶的高通量筛选鉴定出了针对[具体物质1]和[具体物质2]的酰胺类抑制剂。
In Silico Pharmacol. 2018 May 8;6(1):9. doi: 10.1007/s40203-018-0046-4. eCollection 2018.
4
Benzisoxazole: a privileged scaffold for medicinal chemistry.苯并异恶唑:药物化学中的优势骨架。
Medchemcomm. 2017 Oct 31;8(11):2023-2039. doi: 10.1039/c7md00449d. eCollection 2017 Nov 1.
5
Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides.2-(1-苯甲酰基-1H-苯并[d]咪唑-2-基硫代)-N-取代乙酰胺的抗菌、抗结核和抗癌活性的合成与评价
Chem Cent J. 2018 May 26;12(1):66. doi: 10.1186/s13065-018-0432-3.
6
Recent therapeutic approaches for the management of tuberculosis: Challenges and opportunities.最近治疗结核病的方法:挑战与机遇。
Biomed Pharmacother. 2018 Mar;99:735-745. doi: 10.1016/j.biopha.2018.01.115. Epub 2018 Feb 20.
7
New drugs and perspectives for new anti-tuberculosis regimens.新型抗结核治疗方案的新药和新视角。
Pulmonology. 2018 Mar-Apr;24(2):86-98. doi: 10.1016/j.rppnen.2017.10.009. Epub 2018 Feb 24.
8
The Expanding Diversity of Mycobacterium tuberculosis Drug Targets.结核分枝杆菌药物靶点的多样性不断增加。
ACS Infect Dis. 2018 May 11;4(5):696-714. doi: 10.1021/acsinfecdis.7b00255. Epub 2018 Feb 15.
9
Alanine mutation of the catalytic sites of Pantothenate Synthetase causes distinct conformational changes in the ATP binding region.丙氨酸突变泛酸合成酶的催化位点导致 ATP 结合区域的明显构象变化。
Sci Rep. 2018 Jan 17;8(1):903. doi: 10.1038/s41598-017-19075-2.
10
Novel drug targets for Mycobacterium tuberculosis: 2-heterostyrylbenzimidazoles as inhibitors of cell wall protein synthesis.结核分枝杆菌的新型药物靶点:2-杂二苯乙烯基苯并咪唑作为细胞壁蛋白合成抑制剂
Chem Cent J. 2017 Jul 24;11(1):68. doi: 10.1186/s13065-017-0295-z.