Sulfadiazine
Overview
Description
Sulfadiazine is a sulfonamide antibiotic widely used in the treatment of various bacterial infections. It is particularly effective against urinary tract infections, trachoma, and chancroid . This compound is also used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections . This compound is known for its ability to inhibit the synthesis of folic acid in bacteria, thereby preventing their growth and proliferation .
Mechanism of Action
Target of Action
Sulfadiazine primarily targets the bacterial enzyme dihydropteroate synthetase . This enzyme plays a crucial role in the synthesis of folic acid, which is essential for bacterial growth and reproduction .
Mode of Action
This compound acts as a competitive inhibitor of dihydropteroate synthetase . It competes with para-aminobenzoic acid (PABA) for binding to the enzyme, thereby inhibiting the synthesis of folic acid . This results in the inhibition of bacterial growth and reproduction .
Biochemical Pathways
The primary biochemical pathway affected by this compound is the folic acid synthesis pathway in bacteria . By inhibiting dihydropteroate synthetase, this compound prevents the proper processing of PABA, which is essential for folic acid synthesis . This leads to a decrease in the production of folic acid, which is necessary for bacterial growth and reproduction .
Pharmacokinetics
This compound is rapidly and extensively absorbed from the gut and is 20 to 55% bound to plasma proteins . Its elimination half-life is 7-12 hours . This compound can cross the placenta, achieving blood concentrations in the fetus of 50 to 90% of those in the mother . It also achieves high concentrations in breast milk (20% of plasma) .
Result of Action
The primary result of this compound’s action is the inhibition of bacterial growth and reproduction . By inhibiting the synthesis of folic acid, this compound prevents bacteria from growing and reproducing effectively . This makes it an effective treatment for a variety of bacterial infections .
Action Environment
The action of this compound can be influenced by various environmental factors. For example, the presence of pus can inhibit its antibacterial action . The degradation of this compound can be influenced by factors such as temperature, pH, and the presence of certain ions .
Preparation Methods
Synthetic Routes and Reaction Conditions
The synthesis of sulfadiazine typically begins with the acetylation of aniline derivatives using acetic anhydride to form acetanilide derivatives . These derivatives are then reacted with chlorosulfonic acid to produce 4-acetylaminobenzenesulfonyl chloride . In parallel, 2-aminopyrimidine is prepared by reacting tetramethoxypropane with a guanidine salt . The final step involves reacting 4-acetylaminobenzenesulfonyl chloride with 2-aminopyrimidine, followed by hydrolysis with sodium hydroxide to yield this compound .
Industrial Production Methods
Industrial production of this compound follows similar synthetic routes but on a larger scale. The process involves stringent control of reaction conditions to ensure high yield and purity. The use of automated reactors and continuous flow systems helps in maintaining consistent quality and efficiency in production .
Chemical Reactions Analysis
Types of Reactions
Sulfadiazine undergoes various chemical reactions, including oxidation, reduction, and substitution . The compound contains two reactive groups: an aromatic amine and a sulfonamide group, which participate in these reactions .
Common Reagents and Conditions
Oxidation: This compound can be oxidized using reagents like hydrogen peroxide and persulfate under acidic conditions.
Reduction: Reduction of this compound can be achieved using reducing agents such as sodium borohydride.
Substitution: The aromatic amine group in this compound can undergo substitution reactions with electrophiles in the presence of catalysts.
Major Products
The major products formed from these reactions include various derivatives of this compound, which can be further utilized in pharmaceutical applications .
Scientific Research Applications
Sulfadiazine is a sulfonamide antibiotic with various applications in medicine, pharmacology, and other scientific fields . It functions by inhibiting bacteria's ability to produce folic acid, which is essential for DNA synthesis, thereby preventing the spread of infection .
Scientific Research Applications
Antibacterial Agent: this compound is effective against various bacterial infections, including urinary tract infections . It can also be used topically to treat burn and wound infections . The drug inhibits the bacterial enzyme dihydropteroate synthetase, which is crucial for folic acid synthesis .
Treatment of Infections: this compound is used in the treatment of several infections, such as trachoma and chancroid . Laboratory studies on animals have indicated that this compound has less toxicity compared to other drugs like sulfapyridine and sulfathiazole and is highly effective against common pathogens .
Silver this compound in Wound Care: Silver this compound (SSDZ) is a common choice for treating skin burns . It can be integrated into hydrogels for topical wound treatment because hydrogels have minimal toxicity and can sustain the release of pharmaceuticals .
Antimicrobial Properties of Silver Nanoparticles: Silver nanoparticles (AgNPs), including those incorporating silver this compound, have demonstrated antimicrobial properties and have contributed to the development of nanotechnology . AgNPs can potentially replace traditional antibiotics due to increasing bacterial resistance .
Combination Therapies: this compound can be combined with other substances like hyaluronic acid (HA) to treat conditions such as parastomal skin ulceration . The combination of HA and silver this compound has shown success in promoting healing and reducing pain in such cases .
Data Table: Properties and Applications of this compound
Case Studies
Parastomal Ulcer Healing: A case study demonstrated the successful treatment of chronic parastomal skin ulceration using a combination cream of 0.2% Hyaluronic acid and 1% Silver this compound . Patients treated with this combination experienced complete healing, reduced pain, and decreased purulent fluid, leading to a reduced cost of treatment compared to standard protocols .
Silver this compound Hydrogels for Wound Treatment: Silver this compound has been integrated into hydrogels for wound treatment due to the hydrogels' low toxicity and capacity for extended pharmaceutical release .
Research Findings and Insights
Efficacy of Silver this compound: A systematic review comparing Silver this compound with other dressings for burns showed a statistically significant difference in healing time for silver dressings . While some animal studies support the use of Silver this compound for partial-thickness burns, others question its effectiveness .
Toxicity and Safety: Laboratory studies on animals suggest that this compound has lower toxicity compared to sulfapyridine and sulfathiazole .
Comparison with Similar Compounds
Similar Compounds
Sulfamethoxazole: Another sulfonamide antibiotic used in combination with trimethoprim to treat various bacterial infections.
Sulfisoxazole: Used to treat urinary tract infections and other bacterial infections.
Silver sulfadiazine: A topical agent used in the treatment of burns and wound infections.
Uniqueness
This compound is unique due to its broad-spectrum antibacterial activity and its ability to be used in combination with other drugs like pyrimethamine for the treatment of specific infections like toxoplasmosis . Its effectiveness in both human and veterinary medicine further highlights its versatility .
Biological Activity
Sulfadiazine is a sulfonamide antibiotic that has been widely studied for its biological activity, particularly in the treatment of bacterial infections and its potential applications in various medical fields. This article discusses the compound's mechanisms of action, antimicrobial properties, clinical applications, and recent research findings.
This compound functions primarily by inhibiting bacterial folic acid synthesis. It acts as a competitive antagonist of para-aminobenzoic acid (PABA), a substrate required for the synthesis of folate in bacteria. By blocking this pathway, this compound effectively prevents bacterial growth and reproduction, leading to cell death. This mechanism is common among sulfonamides, which have been utilized since their introduction in the 1930s.
Antimicrobial Properties
This compound exhibits a broad spectrum of antimicrobial activity against various pathogens. It has been shown to be effective against:
- Gram-positive bacteria : Staphylococcus aureus, Streptococcus pyogenes
- Gram-negative bacteria : Escherichia coli, Pseudomonas aeruginosa
- Fungi : Candida albicans
- Protozoa : Toxoplasma gondii
Comparative Antimicrobial Efficacy
Recent studies have highlighted the enhanced efficacy of this compound when used in combination with metal complexes. For instance, metal complexes of this compound have demonstrated superior antibacterial activity compared to the free ligand itself, particularly against resistant strains of bacteria .
| Pathogen | Minimum Inhibitory Concentration (MIC) |
|---|---|
| Staphylococcus aureus | 32 µg/mL |
| Escherichia coli | 16 µg/mL |
| Pseudomonas aeruginosa | 64 µg/mL |
| Candida albicans | 8 µg/mL |
Clinical Applications
This compound is commonly used in clinical settings for treating various infections, including:
- Toxoplasmosis : Often administered in combination with pyrimethamine for effective treatment.
- Burn wounds : Silver this compound is a topical formulation used extensively for burn management due to its antimicrobial properties .
Case Studies
-
Silver this compound in Burn Treatment :
A clinical trial involving children with severe burns demonstrated that silver this compound significantly reduced infection rates and facilitated wound healing compared to traditional treatments. The study reported no progression to critical infection stages among treated patients . -
Aerosol Formulation for Pressure Ulcers :
A novel aerosol formulation combining silver this compound with lidocaine and vitamin A showed promising results in treating scalp pressure ulcers in ICU patients. The treatment was associated with improved healing rates and reduced costs compared to conventional dressings .
Recent Research Findings
Recent studies have explored the multifaceted biological activities of this compound beyond its antibacterial properties:
- Anticancer Activity : Research indicates that this compound exhibits antiproliferative effects on human liver cancer (HepG2) and breast cancer (MCF7) cell lines by inhibiting the COX-2/PGE2 signaling pathway. The IC50 values were determined to be approximately 245.69 µM for HepG2 cells and 215.68 µM for MCF7 cells .
- Cytotoxic Effects : this compound derivatives have been synthesized and evaluated for their cytotoxicity against various cancer cell lines, revealing potential as therapeutic agents in oncology .
Properties
IUPAC Name |
4-amino-N-pyrimidin-2-ylbenzenesulfonamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C10H10N4O2S/c11-8-2-4-9(5-3-8)17(15,16)14-10-12-6-1-7-13-10/h1-7H,11H2,(H,12,13,14) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
SEEPANYCNGTZFQ-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1=CN=C(N=C1)NS(=O)(=O)C2=CC=C(C=C2)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C10H10N4O2S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID7044130 |
Source
|
| Record name | Sulfadiazine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID7044130 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
250.28 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 | Sulfadiazine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014503 | |
| 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 |
6.01e-01 g/L |
Source
|
| Record name | Sulfadiazine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00359 | |
| 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 | Sulfadiazine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014503 | |
| 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 |
Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. |
Source
|
| Record name | Sulfadiazine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00359 | |
| 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. |
68-35-9 |
Source
|
| Record name | Sulfadiazine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=68-35-9 | |
| 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 | Sulfadiazine [USP:INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000068359 | |
| 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 | Sulfadiazine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00359 | |
| 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 | sulfadiazine | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=757324 | |
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| Record name | sulfadiazine | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=35600 | |
| 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 | Benzenesulfonamide, 4-amino-N-2-pyrimidinyl- | |
| Source | EPA Chemicals under the TSCA | |
| URL | https://www.epa.gov/chemicals-under-tsca | |
| Description | EPA Chemicals under the Toxic Substances Control Act (TSCA) collection contains information on chemicals and their regulations under TSCA, including non-confidential content from the TSCA Chemical Substance Inventory and Chemical Data Reporting. | |
| Record name | Sulfadiazine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID7044130 | |
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| Record name | Sulfadiazine | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.000.623 | |
| 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. | |
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| Record name | SULFADIAZINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/0N7609K889 | |
| 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. | |
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| Record name | Sulfadiazine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014503 | |
| 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
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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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