二苄基荧光素 | 97744-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 二苄基荧光素
• 英文名称: dibenzylfluorescein
• 英文别名: DBF；O-benzylfluorescein benzyl ester；O,O'-Dibenzylfluorescein；benzyl 2-(3-oxo-6-phenylmethoxyxanthen-9-yl)benzoate
• CAS: 97744-44-0
• 化学式: C₃₄H₂₄O₅
• 分子量: 512.562
• InChiKey: YZJGKSLPSGPFEV-UHFFFAOYSA-N

物化性质

• 熔点：
  >179°C (dec.)
• 溶解度：
  可溶于乙腈

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

二苄基荧光素的已知人类代谢物包括荧光素苄酯和2-[6-(苄氧基)-3-氧代-3H-占吨-9-基]苯甲酸。

Dibenzylfluorescein has known human metabolites that include Fluorescein benzyl ester and 2-[6-(benzyloxy)-3-oxo-3H-xanthen-9-yl]benzoic acid.

来源:NORMAN Suspect List Exchange

安全信息

• 储存条件：
  -20°C，密闭保存，干燥条件

制备方法与用途

二苄基荧光素(DBF)是一种荧光探针，用作特定细胞色素P450(CYP)亚型的底物，包括CYP3A4、CYP2C8、CYP2C9、CYP2C19和芳香化酶(CYP19)。DBF通常在Km值为0.87-1.9 µM（激发波长Ex=485 nm，发射波长Em=535 nm）附近使用。它被用于检测药物或疾病引起的CYP催化活性的变化。

反应信息

• 作为反应物：
  描述：

  二苄基荧光素 在 glucose-6-phosphate dehydrogenase 、 magnesium(II) chloride hexahydrate 、 human liver cytochrome P₄₅₀ isoform 3A₄ 、 nicotinamide adenine dinucleotide phosphate 、 Glucose-6-phosphat Dinatriumsalz 作用下， 以 aq. phosphate buffer 、 乙腈 为溶剂， 反应 0.17h， 生成 fluorescein free acid
  参考文献：
  名称：

  Effects of artemisinin antimalarials on Cytochrome P450 enzymesin vitrousing recombinant enzymes and human liver microsomes: potential implications for combination therapies

  摘要：

  1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug-drug interactions (DDIs).2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC-MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro-in vivo extrapolation using the [I]/K-i ratio was applied to predict the risk of DDI in vivo.3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated with CYP1A2 or 2C19 substrates.4. With respect to CYP1A2 inhibition in vivo by artemisinin compounds, our findings are in line with previously published data. However, reported risks of interaction may be overpredicted and should be interpreted with caution.

  DOI：

  10.3109/00498254.2013.878815
• 作为产物：
  描述：

  fluorescein disodium salt 、 氯化苄 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 二苄基荧光素
  参考文献：
  名称：

  Hargreaves, J. S.; Webber, S. E., Canadian Journal of Chemistry, 1985, vol. 63, p. 1320 - 1327

  摘要：

  DOI：

文献信息

• Molecular design of fluorescent pH sensors based on reduced rhodol by structure-pKa relationship for imaging of lysosome
  作者：Kunal N. More、Seul-Ki Mun、Julie Kang、Jong-Jin Kim、Sung-Tae Yee、Dong-Jo Chang

  DOI：10.1016/j.dyepig.2020.108785

  日期：2021.1

  rhodol and rhodamine, and discovered a reduced rhodol, Rh–OMe, with a methoxy and a free amino group in a xanthene ring. In this work, a series of novel pH-sensitive fluorescent sensors for monitoring acidic lysosomes was developed by structure-pKa relationship study of Rh–OMe. Rh–OMe derivatives with various substituents in an alkoxy group on xanthene ring were designed and evaluated by the analysis

  pH稳态对维持细胞的生存系统至关重要。溶酶体是细胞的消化系统，其中包含许多水解酶，这些水解酶通常可在较弱的酸性pH（4.5-5.5）范围内发挥作用。溶酶体的pH异常会导致溶酶体功能障碍，从而导致多种疾病，例如溶酶体贮积病，癌症，心血管疾病和神经退行性疾病。我们先前报道了一系列还原的x吨荧光团，包括荧光素，Rhodol和若丹明，并发现了还原的Rhodol Rh-OMe，在x吨环中具有甲氧基和游离氨基。在这项工作中，通过Rh-OMe的结构-pKa关系研究，开发了一系列用于监测酸性溶酶体的新型pH敏感荧光传感器。通过分析pH滴定曲线和光化学性质，设计和评估了x吨环烷氧基上具有各种取代基的Rh–OMe衍生物。具有对位取代苄氧基的还原型rhodol探针显示出由酸性pH触发的出色荧光转变，并且已成功地应用于HepG2细胞中溶酶体的体外成像。
• OPTICAL MOLECULAR SENSORS FOR CYTOCHROME P450 ACTIVITY
  申请人：MAKINGS R. Lewis

  公开号：US20070072256A1

  公开（公告）日：2007-03-29

  The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (—OCR 2 H) p —, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

  本发明提供了一种化合物，可用作至少一种细胞色素P450酶活性的光学探针或传感器，并提供了使用该化合物筛选候选药物的方法以及使用这些方法鉴定出的候选药物。本发明的光学探针是一种具有通用结构Y-L-Q的化合物，其中Y选自以下组中的一种：Q如本文所定义的，饱和的C1-C20烷基，不饱和的C1-C20烯基，不饱和的C1-C20炔基，取代的饱和的C1-C20烷基，取代的不饱和的C1-C20烯基，取代的不饱和的C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和的C1-C20环烷基，取代的不饱和的C1-C20环烯基，芳基，取代的芳基，杂环芳基和取代的杂环芳基；L选自（—OCR2H）p—的组中，其中对于每个p，所有的R2分别选自以下组中的一种：氢原子，饱和的C1-C20烷基，不饱和的C1-C20烯基，不饱和的C1-C20炔基，取代的饱和的C1-C20烷基，取代的不饱和的C1-C20烯基，取代的不饱和的C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和的C1-C20环烷基，取代的不饱和的C1-C20环烯基，芳基，取代的芳基，杂环芳基，取代的杂环芳基，p为不大于12的正整数；Q是一种化学基团，在其羟基或羟基化物、酚或酚盐形式下产生的光学性质与其醚形式产生的光学性质不同。最好p为1，R2为氢，Q为酚盐荧光团的醚形式。
• Use of fluorescein aryl ethers in high throughput cytochrome P450 inhibition assays
  申请人：Gentest Corporation

  公开号：US06420131B1

  公开（公告）日：2002-07-16

  Novel fluorescent substrates of human cytochrome P450 enzymes are provided. Also provided are methods for their manufacture and use. These substrates are useful in assessing cytochrome P450 enzyme activity and in selecting compounds which inhibit cytochrome P450 enzyme activity and, in particular, for identifying potential adverse drug interactions which are mediated by inhibition of cytochrome P450 enzyme activity.

  本发明提供了人类细胞色素P450酶的新型荧光底物。同时还提供了其制备和使用的方法。这些底物在评估细胞色素P450酶活性和选择抑制细胞色素P450酶活性的化合物方面非常有用，特别是用于识别通过抑制细胞色素P450酶活性介导的潜在不良药物相互作用。
• Optical molecular sensors for cytochrome P450 activity
  申请人：Makings Lewis R.

  公开号：US20080125586A1

  公开（公告）日：2008-05-29

  The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (—OCR 2 H) p —, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

  该发明提供了一种化合物，可用作至少一种细胞色素P450酶活性的光学探针或传感器，并提供了使用该化合物筛选候选药物的方法，以及由这些方法鉴定的候选药物。该发明的光学探针是一种具有通用结构Y-L-Q的化合物，其中Y选自以下组：Q（如此处定义），饱和C1-C20烷基，不饱和C1-C20烯基，不饱和C1-C20炔基，取代的饱和C1-C20烷基，取代的不饱和C1-C20烯基，取代的不饱和C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和C1-C20环烷基，取代的不饱和C1-C20环烯基，芳基，取代的芳基，杂环芳基和取代的杂环芳基；L选自以下组：（—OCR2H）p—，其中对于每个p，所有R2分别选自以下组：氢原子，饱和C1-C20烷基，不饱和C1-C20烯基，不饱和C1-C20炔基，取代的饱和C1-C20烷基，取代的不饱和C1-C20烯基，取代的不饱和C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和C1-C20环烷基，取代的不饱和C1-C20环烯基，芳基，取代的芳基，杂环芳基，取代的杂环芳基，p为不大于12的正整数；Q是一种化学基团，在其羟基或羟基化物，酚或酚酸盐形式下产生不同于其醚形式的光学性质。最好的情况是，p为1，R2为氢，Q是酚酸盐荧光团的醚形式。
• Optical Molecular Sensors for Cytochrome P450 Activity
  申请人：Makings Lewis R.

  公开号：US20100105095A1

  公开（公告）日：2010-04-29

  The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (—OCR 2 H) p —, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

  本发明提供了一种化合物，可用作至少一种细胞色素P450酶的光学探针或传感器，并提供了使用该化合物筛选候选药物的方法，以及通过这些方法鉴定的候选药物。本发明的光学探针是具有通用结构Y-L-Q的化合物，其中Y选自以下组：Q如本文所定义的，饱和的C1-C20烷基，不饱和的C1-C20烯基，不饱和的C1-C20炔基，取代的饱和的C1-C20烷基，取代的不饱和的C1-C20烯基，取代的不饱和的C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和的C1-C20环烷基，取代的不饱和的C1-C20环烯基，芳基，取代的芳基，杂环芳基和取代的杂环芳基；L选自以下组：（—OCR2H）p—，其中对于每个p，所有R2分别选自以下组：氢原子，饱和的C1-C20烷基，不饱和的C1-C20烯基，不饱和的C1-C20炔基，取代的饱和的C1-C20烷基，取代的不饱和的C1-C20烯基，取代的不饱和的C1-C20炔基，C1-C20环烷基，C1-C20环烯基，取代的饱和的C1-C20环烷基，取代的不饱和的C1-C20环烯基，芳基，取代的芳基，杂环芳基，取代的杂环芳基，p是不大于12的正整数；Q是一种化学基团，在其羟基或羟基酸盐，酚或酚盐形式下产生与其醚形式产生不同的光学性质。最好是，p为1，R2为氢，Q是酚盐荧光团的醚形式。