Albendazole
Übersicht
Beschreibung
Albendazole is a broad-spectrum anthelmintic and antiprotozoal agent belonging to the benzimidazole class of compounds. It is primarily used to treat a variety of parasitic worm infestations, including those caused by roundworms, tapeworms, and flukes . This compound was developed in 1975 and is included in the World Health Organization’s List of Essential Medicines .
Wirkmechanismus
Target of Action
Albendazole is a broad-spectrum anthelmintic . Its primary targets are the intestinal cells and tegument of helminths and their larvae .
Mode of Action
This compound works by binding to the colchicine-sensitive site of tubulin, inhibiting its polymerization or assembly into microtubules . This causes degenerative alterations in the tegument and intestinal cells of the worm by diminishing its energy production, ultimately leading to immobilization and death of the parasite .
Biochemical Pathways
The principal mode of action for this compound is its inhibitory effect on tubulin polymerization, which results in the loss of cytoplasmic microtubules . This disruption of the cytoskeleton leads to the depletion of glycogen stores, impaired glucose uptake, and the accumulation of desecratory substances within the cells of the parasite .
Pharmacokinetics
This compound is metabolized in the liver to its active metabolite, this compound sulfoxide . This metabolite is able to cross the blood-brain barrier and enter the cerebrospinal fluid, allowing it to reach systemic circulation and act as the real antihelminthic . The bioavailability of this compound is less than 5% , and it has a half-life of 8-12 hours . It is excreted through the bile duct in humans .
Result of Action
The result of this compound’s action is the immobilization and death of the parasite . This is due to the degenerative alterations in the tegument and intestinal cells of the worm caused by the drug’s action . This compound is effective against many diseases, including parenchymal neurocysticercosis and other helminth infections .
Action Environment
The efficacy of this compound can be influenced by various factors. For instance, the presence of a fatty meal prior to treatment can increase the systemic availability of this compound sulfoxide, thereby increasing the peak plasma concentration and total exposure following the dose . Additionally, existing parasitic infections can alter the pharmacokinetic parameters of this compound .
Biochemische Analyse
Biochemical Properties
Albendazole interacts with tubulin, a protein that forms the cytoskeleton of cells . By binding to the colchicine-sensitive site of tubulin, this compound inhibits its polymerization or assembly into microtubules . This interaction disrupts the cytoskeleton of the cells, leading to their immobilization and death .
Cellular Effects
This compound has a significant impact on various types of cells and cellular processes. It influences cell function by disrupting the cytoskeleton, which is crucial for cell shape, division, and intracellular transport . This disruption can affect cell signaling pathways, gene expression, and cellular metabolism .
Molecular Mechanism
The principal mode of action for this compound is its inhibitory effect on tubulin polymerization, which results in the loss of cytoplasmic microtubules . This mechanism leads to degenerative alterations in the tegument and intestinal cells of the worm, diminishing its energy production and leading to the immobilization and death of the parasite .
Metabolic Pathways
This compound is involved in metabolic pathways that lead to its transformation into metabolites: this compound sulphoxide (ABZSO) and this compound sulphone (ABZSO2) . These metabolites are formed in the body after administration of this compound .
Vorbereitungsmethoden
Synthetic Routes and Reaction Conditions
Albendazole can be synthesized through several routes. One common method involves the use of 2-nitro-5-chloroaniline as the starting material. This compound undergoes a series of reactions, including substitution, condensation, reduction, and cyclization, to yield this compound . The process avoids the use of high-risk hydrogenation reduction and instead employs an alkali sulfide reduction process, which is safer and more cost-effective .
Industrial Production Methods
In industrial settings, this compound is often produced using a mixed solvent system (water and ethanol) and a mixed acid system (formic acid and acetic acid) for refinement. This method results in this compound with higher purity and solubility . Additionally, this compound can be formulated into colon-targeted microcapsules to enhance its absorption and efficacy .
Analyse Chemischer Reaktionen
Arten von Reaktionen
Albendazol unterliegt verschiedenen chemischen Reaktionen, darunter Oxidation, Reduktion und Substitution.
Häufige Reagenzien und Bedingungen
Reduktion: Der Reduktionsprozess bei der Synthese von Albendazol beinhaltet die Verwendung von Alkalisulfid.
Substitution: Die anfängliche Substitutionsreaktion bei der Synthese beinhaltet 2-Nitro-5-Chloranilin und halogeniertes n-Propan.
Hauptprodukte
Wissenschaftliche Forschungsanwendungen
Albendazol hat ein breites Anwendungsspektrum in der wissenschaftlichen Forschung:
Chemie: Es wird als Modellverbindung in Studien mit Benzimidazolderivaten verwendet.
Wirkmechanismus
Albendazol entfaltet seine Wirkung, indem es an die colchicinsensitive Stelle von Tubulin bindet und so dessen Polymerisation zu Mikrotubuli hemmt. Diese Störung der Mikrotubuli-Bildung führt zu degenerativen Veränderungen in den Darmepithelzellen der Parasiten, was letztendlich zu deren Tod führt . Das primäre molekulare Ziel ist Tubulin, und der beteiligte Weg ist die Hemmung der Mikrotubuli-Polymerisation .
Vergleich Mit ähnlichen Verbindungen
Albendazol wird häufig mit anderen Benzimidazol-Anthelminthika wie Mebendazol und Fenbendazol verglichen. Obwohl alle drei Verbindungen einen ähnlichen Wirkmechanismus aufweisen, zeichnet sich Albendazol durch sein breiteres Wirkungsspektrum und seine höhere Wirksamkeit gegen bestimmte parasitäre Infektionen aus .
Ähnliche Verbindungen
Eigenschaften
IUPAC Name |
methyl N-(6-propylsulfanyl-1H-benzimidazol-2-yl)carbamate |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C12H15N3O2S/c1-3-6-18-8-4-5-9-10(7-8)14-11(13-9)15-12(16)17-2/h4-5,7H,3,6H2,1-2H3,(H2,13,14,15,16) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
HXHWSAZORRCQMX-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCCSC1=CC2=C(C=C1)N=C(N2)NC(=O)OC |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C12H15N3O2S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID0022563 |
Source
|
| Record name | Albendazole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID0022563 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
265.33 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 | Albendazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014659 | |
| 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 |
1.4 [ug/mL] (The mean of the results at pH 7.4), Practically insoluble, 2.28e-02 g/L |
Source
|
| Record name | SID855809 | |
| Source | Burnham Center for Chemical Genomics | |
| URL | https://pubchem.ncbi.nlm.nih.gov/bioassay/1996#section=Data-Table | |
| Description | Aqueous solubility in buffer at pH 7.4 | |
| Record name | Albendazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00518 | |
| 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 | Albendazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014659 | |
| 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 |
Albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by diminishing its energy production, ultimately leading to immobilization and death of the parasite. It works by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. As cytoplasmic microtubules are critical in promoting glucose uptake in larval and adult stages of the susceptible parasites, the glycogen stores of the parasites are depleted. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth., Benzimidazoles produce many biochemical changes in susceptible nematodes, eg, inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation ... /but/ the primary action ... /should be/ to inhibit microtubule polymerization by binding to beta-tubulin. The selective toxicity of these agents derives from the fact that specific, high-affinity binding to parasite beta-tubulin occurs at much lower concn than does binding to the mammalian protein ... Benzimidazole-resistant Haemonchus contortus display reduced high-affinity drug binding to beta-tubulin and alterations in beta-tubulin isotype gene expression that correlate with drug resistance ... Two identified mechanisms of drug resistance in nematodes involve both a progressive loss of "susceptible" beta-tubulin gene isotypes together with emergence of a "resistant" isotype with a conserved point mutation that encodes a tyrosine instead of phenylalanine at position 200 of beta-tubulin. While this mutation may not be required for benzimidazole resistance in all parasites, eg, Giardia lamblia, benzimidazole resistance in parasitic nematodes is unlikely to be overcome by novel benzimidazole analogs, because tyrosine also is present at position 200 of human beta-tubulin. /Benzimidazoles/, Although the exact mechanism of action of albendazole has not been fully elucidated, the principal anthelmintic effect of benzimidazoles, including albendazole, appears to be the specific, high-affinity binding of the drug to free beta-tubulin in parasite cells, resulting in selective inhibition of parasite microtubule polymerization, and inhibition of microtubule-dependent uptake of glucose. Benzimidazole drugs bind to the beta-tubulin of parasites at much lower concentrations than to mammalian beta-tubulin protein; the drugs do not inhibit glucose uptake in mammals, and do not appear to have any effect on blood glucose concentrations in humans, The mode of action of albendazole is by binding strongly with the tubulin in the cells of nematodes. The intestinal cells of the nematode are particularly affected, resulting in a loss of absorptive function which causes the nematodes to starve to death. |
Source
|
| Record name | Albendazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00518 | |
| 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. | |
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| Record name | ALBENDAZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7444 | |
| 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 |
Colorless crystals | |
CAS No. |
54965-21-8 |
Source
|
| Record name | Albendazole | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=54965-21-8 | |
| 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 | Albendazole [USAN:USP:INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0054965218 | |
| 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 | Albendazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00518 | |
| 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 | albendazole | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=758644 | |
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| Record name | albendazole | |
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| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=220008 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
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| Record name | Albendazole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID0022563 | |
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| Record name | Albendazole | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.053.995 | |
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| Record name | ALBENDAZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7444 | |
| 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. | |
| Record name | Albendazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014659 | |
| 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. | |
Melting Point |
208-210, 208-210 °C, Mol wt: 281.34. Active metabolite of albendazole. MP: 226-228 °C (decomposes) /Sulfoxide/, 209 °C |
Source
|
| Record name | Albendazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00518 | |
| 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 | ALBENDAZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7444 | |
| 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. | |
| Record name | Albendazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014659 | |
| 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. | |
Synthesis routes and methods I
Procedure details
Synthesis routes and methods II
Procedure details
Retrosynthesis Analysis
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| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
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Feasible Synthetic Routes
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