Paromomycin
Übersicht
Beschreibung
Paromomycin is an aminoglycoside antibiotic that is primarily used to treat various parasitic infections, including amebiasis, giardiasis, leishmaniasis, and tapeworm infections . It was discovered in the 1950s from a type of Streptomyces and came into medical use in 1960 . This compound is on the World Health Organization’s List of Essential Medicines .
Wissenschaftliche Forschungsanwendungen
Paromomycin has a wide range of scientific research applications:
Wirkmechanismus
Target of Action
Paromomycin primarily targets the 16S ribosomal RNA of bacteria . This RNA is a component of the small (30S) subunit of the bacterial ribosome, which is involved in protein synthesis .
Mode of Action
This compound inhibits protein synthesis by binding to the 16S ribosomal RNA . The bacterial proteins are synthesized by ribosomal RNA complexes, which are composed of two subunits, a large subunit (50S) and a small (30S) subunit, forming a 70S ribosomal subunit . The tRNA binds to the top of this ribosomal structure . By binding to the 16S ribosomal RNA, this compound interferes with this process, leading to the production of defective proteins .
Biochemical Pathways
It is known that the drug interferes with protein synthesis, which is a crucial process for bacterial survival . This interference leads to the production of defective proteins, which can disrupt various cellular functions and eventually lead to bacterial death .
Pharmacokinetics
This compound is poorly absorbed in the gastrointestinal tract . This characteristic makes it particularly useful for treating intestinal infections, as the drug remains in the gut where it can act directly on the infecting organisms . The drug is excreted in feces .
Result of Action
The primary result of this compound’s action is the death of the bacteria. By inhibiting protein synthesis, this compound causes the production of defective proteins. The accumulation of these defective proteins disrupts various cellular functions, leading to bacterial death .
Action Environment
The action of this compound is influenced by the environment in which it is used. For instance, in the gastrointestinal tract, where it is poorly absorbed, this compound can act directly on the infecting organisms . .
Biochemische Analyse
Biochemical Properties
Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA . This interaction with the ribosomal RNA complexes, which are composed of two subunits, disrupts the formation of bacterial proteins . The nature of these interactions is such that it closely parallels the in vitro and in vivo antibacterial action of neomycin .
Cellular Effects
This compound has a broad spectrum of activity against various types of cells, including Gram-negative and Gram-positive bacteria . It increases the error rate in ribosomal translation, leading to the production of defective polypeptide chains . This continuous production of defective proteins eventually leads to bacterial death .
Molecular Mechanism
The mechanism of action of this compound involves its binding to a RNA loop, where residues A1492 and A1493 are usually stacked, and expels these two residues . These two residues are involved in the detection of correct Watson-Crick pairing between the codon and anti-codon .
Temporal Effects in Laboratory Settings
The effects of this compound over time in laboratory settings have not been extensively studied. It is known that the most common adverse effects associated with this compound sulfate are abdominal cramps, diarrhea, heartburn, nausea, and vomiting . Long-term use of this compound increases the risk for bacterial or fungal infection .
Dosage Effects in Animal Models
The effects of this compound vary with different dosages in animal models . For example, it has been shown to be effective at a dosage of 50mg/kg/day or more for ileal infection and 200mg/kg/day or more for caecal infection . The effect was thus shown to differ according to the anatomical site of the infection .
Metabolic Pathways
The metabolic pathways that this compound is involved in primarily relate to its role as an aminoglycoside antibiotic. It inhibits protein synthesis by binding to 16S ribosomal RNA
Transport and Distribution
This compound is poorly absorbed after oral administration, with almost 100% of the drug recoverable in the stool This suggests that its transport and distribution within cells and tissues are limited
Vorbereitungsmethoden
Paromomycin is produced by the bacterium Streptomyces rimosus var. paromomycinus . The industrial production of this compound typically involves fermentation processes. Solid-state fermentation has been shown to be a promising method for producing this compound, offering advantages such as cost reduction of raw materials, less energy consumption, and reduced wastewater discharge . The optimization of environmental conditions, such as pH, temperature, and inoculum size, can significantly enhance the yield of this compound .
Analyse Chemischer Reaktionen
Paromomycin undergoes various chemical reactions, including oxidation and substitution reactions. The compound contains oxidizable groups such as amines and hydroxyls, which can be detected electrochemically . Common reagents used in these reactions include oxidizing agents and derivatization agents for detection purposes. The major products formed from these reactions depend on the specific conditions and reagents used.
Vergleich Mit ähnlichen Verbindungen
Paromomycin is similar to other aminoglycoside antibiotics such as neomycin and streptomycin . it has unique properties that make it effective against a broader range of parasitic infections. Unlike some other aminoglycosides, this compound is poorly absorbed in the gastrointestinal tract, making it particularly useful for treating intestinal infections . Additionally, this compound has been shown to have fewer systemic side effects compared to pentavalent antimony compounds used in the treatment of leishmaniasis .
Similar Compounds
- Neomycin
- Streptomycin
- Gentamicin
- Tobramycin
This compound’s unique properties and broad-spectrum activity make it a valuable antibiotic in both clinical and research settings.
Eigenschaften
IUPAC Name |
(2S,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(2R,3S,4R,5S)-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C23H45N5O14/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22/h5-23,29-36H,1-4,24-28H2/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
UOZODPSAJZTQNH-LSWIJEOBSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1C(C(C(C(C1N)OC2C(C(C(C(O2)CO)O)O)N)OC3C(C(C(O3)CO)OC4C(C(C(C(O4)CN)O)O)N)O)O)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O[C@@H]4[C@@H]([C@H]([C@@H]([C@@H](O4)CN)O)O)N)O)O)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C23H45N5O14 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
1263-89-4 (sulfate), 35665-49-7 (sulfate (2:5)), 7205-49-4 (sulfate (1:1)) |
Source
|
| Record name | Paromomycin [INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0007542372 | |
| 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. | |
DSSTOX Substance ID |
DTXSID8023424 |
Source
|
| Record name | Paromomycin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023424 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
615.6 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Paromomycin | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015490 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
7.97e+01 g/L |
Source
|
| Record name | Paromomycin | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015490 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA. Bacterial proteins are synthesized by ribosomal RNA complexes which are composed of 2 subunits, a large subunit (50s) and small (30s) subunit, which forms a 70s ribosomal subunit. tRNA binds to the top of this ribosomal structure. Paramomycin binds to the A site, which causes defective polypeptide chains to be produced. Continuous production of defective proteins eventually leads to bacterial death. |
Source
|
| Record name | Paromomycin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01421 | |
| 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) | |
CAS No. |
7542-37-2, 1263-89-4 |
Source
|
| Record name | Paromomycin | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=7542-37-2 | |
| 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 | Paromomycin [INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0007542372 | |
| 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 | Paromomycin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01421 | |
| 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 | Paromomycin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023424 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Paromomycin | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.028.567 | |
| 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 | PAROMOMYCIN | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/61JJC8N5ZK | |
| 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 | Paromomycin | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015490 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
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