TB501 | 899387-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: TB501
• 英文别名: 7-[[4-(2-Hydroxyethyl)piperazin-1-ium-1-yl]methyl]-2-[3-(2-methoxyphenyl)prop-2-enylidene]-3-oxo-1-benzofuran-6-olate；7-[[4-(2-hydroxyethyl)piperazin-1-ium-1-yl]methyl]-2-[3-(2-methoxyphenyl)prop-2-enylidene]-3-oxo-1-benzofuran-6-olate
• CAS: 899387-20-3
• 化学式: C₂₅H₂₈N₂O₅
• 分子量: 436.508
• InChiKey: DGBDTVNISBOCDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  戊二酸酐 、 TB501 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以68%的产率得到pentanedioic acid mono-[2-(4-{6-hydroxy-2-[3-(2-methoxyphenyl)-allylidene]-3-oxo-2,3-dihydro-benzofuran-7-ylmethyl}-piperazin-1-yl)-ethyl] ester
  参考文献：
  名称：

  Enhanced Cellular Uptake of a New, in Silico Identified Antitubercular Candidate by Peptide Conjugation

  摘要：

  Mycobacterium tuberculosis is a successful pathogen, and it can survive in infected macrophages in dormant phase for years and decades. The therapy of tuberculosis takes at least six months, and the slow-growing bacterium is resistant to many antibiotics. The development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies is urgently needed. In silico docking methods and structure-based drug design are useful bioinformatics tools for identifying new agents. A docking experiment to M. tuberculosis dUTPase enzyme, which plays a key role in the bacterial metabolism, has resulted in 10 new antitubercular drug candidates. The uptake of antituberculars by infected macrophages is limited by extracellular diffusion. The optimization of the cellular uptake by drug delivery systems can decrease the used dosages and the length of the therapy, and it can also enhance the bioavailability of the drug molecule. In this study, improved in vitro efficacy was achieved by attaching the TB5 antitubercular drug candidate to peptide carriers. As drug delivery components, (i) an antimicrobial granulysin peptide and (ii) a receptor specific tuftsin peptide were used. An efficient synthetic approach was developed to conjugate the in silica identified TB5 coumarone derivative to the carrier peptides. The compounds were effective on M. tuberculosis H(37)Rv culture in vitro; the chemical linkage did not affect the antimycobacterial activity. Here, we show that the OT20 tuftsin and GranF2 granulysin peptide conjugates have dramatically enhanced uptake into human MonoMac6 cells. The TB5-OT20 tuftsin conjugate exhibited significant antimycobacterial activity on M. tuberculosis H(37)Rv infected MonoMac6 cells and inhibited intracellular bacteria.

  DOI：

  10.1021/bc200221t

文献信息

• Enhanced Cellular Uptake of a New, <i>in Silico</i> Identified Antitubercular Candidate by Peptide Conjugation
  作者：Kata Horváti、Bernadett Bacsa、Nóra Szabó、Sándor Dávid、Gábor Mező、Vince Grolmusz、Beáta Vértessy、Ferenc Hudecz、Szilvia Bősze

  DOI：10.1021/bc200221t

  日期：2012.5.16

  Mycobacterium tuberculosis is a successful pathogen, and it can survive in infected macrophages in dormant phase for years and decades. The therapy of tuberculosis takes at least six months, and the slow-growing bacterium is resistant to many antibiotics. The development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies is urgently needed. In silico docking methods and structure-based drug design are useful bioinformatics tools for identifying new agents. A docking experiment to M. tuberculosis dUTPase enzyme, which plays a key role in the bacterial metabolism, has resulted in 10 new antitubercular drug candidates. The uptake of antituberculars by infected macrophages is limited by extracellular diffusion. The optimization of the cellular uptake by drug delivery systems can decrease the used dosages and the length of the therapy, and it can also enhance the bioavailability of the drug molecule. In this study, improved in vitro efficacy was achieved by attaching the TB5 antitubercular drug candidate to peptide carriers. As drug delivery components, (i) an antimicrobial granulysin peptide and (ii) a receptor specific tuftsin peptide were used. An efficient synthetic approach was developed to conjugate the in silica identified TB5 coumarone derivative to the carrier peptides. The compounds were effective on M. tuberculosis H(37)Rv culture in vitro; the chemical linkage did not affect the antimycobacterial activity. Here, we show that the OT20 tuftsin and GranF2 granulysin peptide conjugates have dramatically enhanced uptake into human MonoMac6 cells. The TB5-OT20 tuftsin conjugate exhibited significant antimycobacterial activity on M. tuberculosis H(37)Rv infected MonoMac6 cells and inhibited intracellular bacteria.