テニポシド
概要
説明
作用機序
テニポシドは、DNA複製と細胞分裂に不可欠な酵素であるトポイソメラーゼIIを阻害することで効果を発揮します . テニポシドは、トポイソメラーゼIIとDNAに複合体を形成することによって、二本鎖DNAの切断を引き起こし、修復を阻止し、細胞死を誘導します . このメカニズムは、主に細胞周期のG2期とS期にある細胞に影響を与えます .
類似の化合物：
エトポシド： 作用機序が類似した別のポドフィロトキシン誘導体です.
ポドフィロトキシン： テニポシドが誘導される親化合物です.
比較：
エトポシド対テニポシド： 両方の化合物はトポイソメラーゼIIを阻害しますが、テニポシドはより高い中枢神経系への浸透性とより高い親油性を持っています.
ポドフィロトキシン対テニポシド： ポドフィロトキシンは天然の前駆体である一方、テニポシドは化学的に修飾されて治療効果を高め、毒性を低下させています.
テニポシドの独特の特性、例えば高い親油性と高い中枢神経系への浸透性は、類似の化合物に比べて明確な利点を持つ貴重な化学療法薬としてテニポシドを位置付けています .
科学的研究の応用
Teniposide has a wide range of scientific research applications:
Chemistry: Used as a model compound to study the mechanisms of topoisomerase II inhibition.
Biology: Investigated for its effects on cell cycle regulation and apoptosis.
Industry: Utilized in the development of new chemotherapeutic agents and drug delivery systems.
生化学分析
Biochemical Properties
Teniposide plays a significant role in biochemical reactions. It interacts with topoisomerase II, a crucial enzyme involved in DNA replication and transcription . The interaction between Teniposide and topoisomerase II is complex, leading to breaks in double-stranded DNA and preventing repair by topoisomerase II binding .
Cellular Effects
Teniposide has profound effects on various types of cells and cellular processes. It influences cell function by inducing breaks in double-stranded DNA, which can impact cell signaling pathways, gene expression, and cellular metabolism .
Molecular Mechanism
The mechanism of action of Teniposide involves forming a complex with topoisomerase II and DNA . This complex induces breaks in double-stranded DNA and prevents repair by topoisomerase II binding . This action at the molecular level can lead to changes in gene expression and potentially result in cell death, particularly in cancer cells .
Metabolic Pathways
Teniposide is involved in the metabolic pathway related to DNA synthesis . It interacts with the enzyme topoisomerase II during this process .
Transport and Distribution
Given its mechanism of action, it’s likely that it interacts with transporters or binding proteins involved in DNA synthesis and repair .
Subcellular Localization
Given its interaction with topoisomerase II, it’s likely localized to areas of the cell where DNA synthesis and repair occur .
準備方法
合成経路と反応条件： テニポシドはポドフィロトキシンの半合成誘導体です。 合成には、ポドフィロトキシンをD-グルコース誘導体でグリコシル化する工程が含まれます . 反応条件には、一般的に、グリコシル化プロセスを促進するために酸性または塩基性の触媒を使用することが含まれます。
工業生産方法： テニポシドの工業生産には、野生マンドレイク（Podophyllum peltatum）の根茎からのポドフィロトキシンを大規模に抽出する工程と、化学修飾によってテニポシドを生成する工程が含まれます . このプロセスは、最終製品の高収率と純度を確保するために最適化されています。
化学反応の分析
反応の種類： テニポシドは、以下を含むさまざまな化学反応を起こします。
酸化： テニポシドは酸化されて反応性の中間体を形成する可能性があります。
還元： 還元反応は、テニポシドの官能基を修飾できます。
置換： テニポシド分子の特定の部位で置換反応が起こる可能性があります。
一般的な試薬と条件：
酸化剤： 過酸化水素、過マンガン酸カリウム。
還元剤： 水素化ホウ素ナトリウム、水素化リチウムアルミニウム。
置換試薬： ハロゲン、求核剤。
主な生成物： これらの反応から形成される主な生成物は、使用される特定の試薬と条件によって異なります。 例えば、酸化はキノンを生成し、還元はアルコールまたはアミンを生成する可能性があります。
4. 科学研究の応用
テニポシドは、幅広い科学研究の応用を持っています。
化学： トポイソメラーゼII阻害のメカニズムを研究するためのモデル化合物として使用されています。
生物学： 細胞周期調節とアポトーシスに対するその影響について調査されています。
類似化合物との比較
Etoposide: Another podophyllotoxin derivative with a similar mechanism of action.
Podophyllotoxin: The parent compound from which teniposide is derived.
Comparison:
Etoposide vs. Teniposide: Both compounds inhibit topoisomerase II, but teniposide has greater central nervous system penetrance and is more lipophilic.
Podophyllotoxin vs. Teniposide: While podophyllotoxin is the natural precursor, teniposide is chemically modified to improve its therapeutic efficacy and reduce toxicity.
Teniposide’s unique properties, such as its higher lipophilicity and greater central nervous system penetrance, make it a valuable chemotherapeutic agent with distinct advantages over similar compounds .
特性
IUPAC Name |
(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-thiophen-2-yl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C32H32O13S/c1-37-19-6-13(7-20(38-2)25(19)33)23-14-8-17-18(42-12-41-17)9-15(14)28(16-10-39-30(36)24(16)23)44-32-27(35)26(34)29-21(43-32)11-40-31(45-29)22-4-3-5-46-22/h3-9,16,21,23-24,26-29,31-35H,10-12H2,1-2H3/t16-,21+,23+,24-,26+,27+,28+,29+,31+,32-/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
NRUKOCRGYNPUPR-QBPJDGROSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
COC1=CC(=CC(=C1O)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)OC6C(C(C7C(O6)COC(O7)C8=CC=CS8)O)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
COC1=CC(=CC(=C1O)OC)[C@H]2[C@@H]3[C@H](COC3=O)[C@@H](C4=CC5=C(C=C24)OCO5)O[C@H]6[C@@H]([C@H]([C@H]7[C@H](O6)CO[C@H](O7)C8=CC=CS8)O)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C32H32O13S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID8023638 |
Source
|
| Record name | Teniposide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023638 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
656.7 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Solubility |
Practically insoluble in water., In water, 5.9 mg/L at 25 °C /Estimated/ |
Source
|
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Vapor Pressure |
6.8X10-26 mm Hg at 25 °C /Estimated/ |
Source
|
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Mechanism of Action |
The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate., It is an inhibitor of DNA topoisomerase II enzymes: Teniposide is a DNA topoisomerase II poison that has been shown to promote DNA cleavage, with a strong preference for a C or T at position -1. Most of the mutational events reported in mammalian cells, including point mutations, chromosomal deletions and exchanges and aneuploidy, can be explained by this activity. Teniposide does not inhibit bacterial topoisomerases and may not mutate bacterial cells by the same mechanism as mammalian cells. Unlike many other DNA topoisomerase II poisons, teniposide does not bind to DNA, either covalently or by intercalation. Instead, it appears to interact directly with the DNA topoisomerase II enzyme., ... The drug appears to produce its cytotoxic effects by damaging DNA and thereby inhibiting or altering DNA synthesis. Teniposide has been shown to induce single-stranded DNA breaks; the drug also induces double-stranded DNA breaks and DNA-protein cross links. ... Teniposide appears to be cell cycle specific, inducing G2-phase arrest and preferentially killing cells in the G2 and late S phases. |
Source
|
| Record name | Teniposide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00444 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Impurities |
... The 50-mg intravenous preparation typically also contains benzyl alcohol (0.15 g), N,N-dimethylacetamide (0.3 g), polyethoxylated castor oil (2.5 g), maleic acid to a pH of 5.1 and absolute ethanol to 5 mL. |
Source
|
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Color/Form |
Crystals from absolute ethanol | |
CAS No. |
29767-20-2 |
Source
|
| Record name | Teniposide | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=29767-20-2 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Teniposide [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0029767202 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Teniposide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00444 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Teniposide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023638 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Teniposide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.045.286 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | TENIPOSIDE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/957E6438QA | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Melting Point |
242-246 °C |
Source
|
| Record name | Teniposide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00444 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | TENIPOSIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/6546 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
試験管内研究製品の免責事項と情報
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