Cefixime
Overview
Description
Cefixime is a third-generation cephalosporin antibiotic used to treat a variety of bacterial infections. It is effective against both Gram-positive and Gram-negative bacteria. This compound works by inhibiting the synthesis of the bacterial cell wall, leading to cell lysis and death. It is commonly used to treat infections such as otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme disease .
Mechanism of Action
Target of Action
Cefixime, a third-generation cephalosporin, primarily targets the penicillin-binding proteins (PBPs) . These proteins are a family of enzymes involved in the synthesis and remodeling of the bacterial cell wall, specifically the glycopeptide polymer known as peptidoglycan .
Mode of Action
This compound interacts with its targets, the PBPs, by binding to them . This binding inhibits the PBPs, which are essential for maintaining cell wall homeostasis . The β-lactam ring of this compound is responsible for this inhibition . The inhibition of these enzymes disrupts the final 3D structure of the bacterial cell wall, thereby inhibiting bacterial cell wall peptidoglycan synthesis .
Biochemical Pathways
The primary biochemical pathway affected by this compound is the synthesis of the bacterial cell wall. By inhibiting the PBPs, this compound disrupts the synthesis of peptidoglycan, a critical component of the bacterial cell wall . This disruption leads to impaired cell wall homeostasis, loss of cell integrity, and ultimately, bacterial cell death .
Pharmacokinetics
After a 200 mg intravenous or oral dose, the absolute bioavailability of this compound is 50% . It can be taken with or without meals, indicating that food has no effect on peak serum concentrations or the extent of drug absorption .
Result of Action
The primary result of this compound’s action is the lysis of bacterial cells . By inhibiting the synthesis of the bacterial cell wall, this compound causes the bacteria to lose their structural integrity . This leads to the rupture of the bacterial cell wall and the death of the bacteria .
Action Environment
The action of this compound can be influenced by various environmental factors. For instance, the degradation efficiency of this compound can be affected by factors such as pH, contact time, pollutant concentration, and catalyst dosage . Additionally, the release of cephalosporin antibiotics like this compound into the environment can have significant impacts due to the excretion of a large percentage of unchanged antibiotics that remain bioactive in soil-water ecosystems .
Safety and Hazards
Preparation Methods
Synthetic Routes and Reaction Conditions: Cefixime is synthesized through a multi-step process involving the condensation of 7-aminocephalosporanic acid with various side chains. The key steps include:
Acylation: The 7-amino group of 7-aminocephalosporanic acid is acylated with a suitable acylating agent.
Cyclization: The acylated intermediate undergoes cyclization to form the β-lactam ring.
Side Chain Introduction: The side chain is introduced through nucleophilic substitution reactions.
Industrial Production Methods: Industrial production of this compound involves large-scale fermentation processes to produce 7-aminocephalosporanic acid, followed by chemical synthesis to introduce the side chains. The process is optimized for high yield and purity, involving steps such as crystallization, filtration, and drying .
Chemical Reactions Analysis
Types of Reactions: Cefixime undergoes several types of chemical reactions, including:
Oxidation: this compound can be oxidized to form sulfoxides and sulfones.
Reduction: Reduction reactions can convert this compound to its corresponding amine derivatives.
Substitution: Nucleophilic substitution reactions can modify the side chains of this compound.
Common Reagents and Conditions:
Oxidation: Hydrogen peroxide or peracids are commonly used oxidizing agents.
Reduction: Sodium borohydride or catalytic hydrogenation are typical reducing conditions.
Substitution: Nucleophiles such as amines or thiols are used under basic conditions.
Major Products:
Oxidation: Sulfoxides and sulfones.
Reduction: Amine derivatives.
Substitution: Modified cephalosporin derivatives
Scientific Research Applications
Cefixime has a wide range of scientific research applications:
Chemistry: Used as a model compound to study β-lactam antibiotics and their interactions with bacterial enzymes.
Biology: Investigated for its effects on bacterial cell wall synthesis and resistance mechanisms.
Medicine: Extensively used in clinical trials to evaluate its efficacy against various bacterial infections.
Industry: Utilized in the development of new antibiotic formulations and drug delivery systems
Comparison with Similar Compounds
- Ceftriaxone
- Cefotaxime
- Ceftazidime
- Cefepime
- Cefuroxime
Properties
IUPAC Name |
7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid |
Source
|
|---|---|---|
| Details | Computed by Lexichem TK 2.7.0 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C16H15N5O7S2/c1-2-6-4-29-14-10(13(25)21(14)11(6)15(26)27)19-12(24)9(20-28-3-8(22)23)7-5-30-16(17)18-7/h2,5,10,14H,1,3-4H2,(H2,17,18)(H,19,24)(H,22,23)(H,26,27) |
Source
|
| Details | Computed by InChI 1.0.6 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
OKBVVJOGVLARMR-UHFFFAOYSA-N |
Source
|
| Details | Computed by InChI 1.0.6 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C=CC1=C(N2C(C(C2=O)NC(=O)C(=NOCC(=O)O)C3=CSC(=N3)N)SC1)C(=O)O |
Source
|
| Details | Computed by OEChem 2.3.0 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C16H15N5O7S2 |
Source
|
| Details | Computed by PubChem 2.1 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID20861014 |
Source
|
| Record name | 7-{2-(2-Amino-1,3-thiazol-4-yl)[(carboxymethoxy)imino]acetamido}-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID20861014 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
453.5 g/mol |
Source
|
| Details | Computed by PubChem 2.1 (PubChem release 2021.05.07) | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
CAS No. |
79350-37-1 |
Source
|
| Record name | 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2Z)-2-(2-amino-4-thiazolyl)-2-[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl-8-oxo-, (6R,7R) | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.119.331 | |
| 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. | |
Retrosynthesis Analysis
AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.
One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.
Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.
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
Q1: How does cefixime exert its antibacterial effect?
A1: this compound, like other β-lactam antibiotics, targets penicillin-binding proteins (PBPs) located within the bacterial cell wall [, ]. These proteins are crucial enzymes involved in the final stages of peptidoglycan synthesis, a vital component of the bacterial cell wall. By binding to PBPs, this compound disrupts the cross-linking of peptidoglycan strands, ultimately leading to bacterial cell death [].
Q2: What is the chemical formula and molecular weight of this compound?
A2: this compound trihydrate's molecular formula is C16H15N5O7S2 • 3H2O, and its molecular weight is 493.48 g/mol. []
Q3: Are there any spectroscopic techniques used to characterize this compound?
A3: Yes, various spectroscopic techniques have been employed to characterize this compound, including FTIR (Fourier-transform infrared spectroscopy), DSC (Differential Scanning Calorimetry), and XRD (X-ray diffraction) [, ]. These techniques provide valuable information about the drug's chemical structure, purity, and physical properties, which are essential for formulation development and quality control.
Q4: Are there specific excipients that enhance this compound's stability?
A5: Studies have shown that complexation with Captisol (sulfobutylether β-cyclodextrin) and the addition of hypromellose significantly improve this compound's stability against aqueous-mediated degradation []. This finding highlights the importance of excipient selection in ensuring optimal drug stability.
Q5: What is the bioavailability of this compound after oral administration?
A6: this compound is marketed as an orally active antibiotic, but its bioavailability can be influenced by various factors. Studies in healthy volunteers have shown that its bioavailability can be affected by the formulation and the presence of other drugs [, ].
Q6: How does the co-administration of other drugs impact this compound's pharmacokinetics?
A7: Research indicates that drugs like nifedipine, omeprazole, rosuvastatin, and clopidogrel can alter the pharmacokinetic parameters of this compound [, ]. For instance, nifedipine has been shown to increase this compound absorption in a rat intestinal perfusion model, suggesting potential neural regulation of this interaction []. These interactions highlight the importance of considering potential drug-drug interactions when prescribing this compound.
Q7: Are there strategies to improve the solubility of this compound?
A9: Researchers have explored various techniques to enhance this compound solubility, including solid dispersion technology, hydrotropic solubilization, and the development of liquisolid systems [, , ]. These strategies aim to increase the drug's solubility and dissolution rate, ultimately improving its bioavailability and therapeutic efficacy.
Q8: What are the major mechanisms of resistance to this compound in Neisseria gonorrhoeae?
A10: The emergence of Neisseria gonorrhoeae strains with reduced susceptibility to this compound poses a significant threat to gonorrhea treatment. This reduced susceptibility is often linked to mutations in specific genes, including penA, mtrR, porB1b (penB), and ponA [, ].
Q9: What is the significance of the penA mosaic allele in this compound resistance?
A11: The penA gene encodes PBP2, the primary target of this compound. The presence of penA mosaic alleles, characterized by specific amino acid substitutions in PBP2, is strongly associated with decreased susceptibility to this compound and ceftriaxone [, ]. These mutations can alter the binding affinity of this compound to PBP2, rendering the drug less effective.
Q10: What analytical methods are used to measure this compound concentrations?
A12: Several analytical methods have been developed and validated for the accurate quantification of this compound in various matrices, including serum, cerebrospinal fluid, and pharmaceutical formulations [, , ]. High-performance liquid chromatography (HPLC) coupled with UV detection is widely employed for this compound analysis, offering high sensitivity and selectivity [, , ]. Researchers have also developed first-order derivative spectrophotometric methods for simultaneous determination of this compound in combination with other drugs like linezolid [].
Q11: What are some challenges in the development of analytical methods for this compound?
A13: One challenge is ensuring the method's stability-indicating capability, meaning it can differentiate this compound from its degradation products []. This is crucial for accurate drug quantification in stability studies and quality control of pharmaceutical formulations.
Q12: Have there been efforts to improve this compound delivery to specific sites of infection?
A14: While most research on this compound focuses on its oral formulation and systemic delivery, some studies explore alternative delivery routes. For instance, this compound suppositories have been investigated as a potential approach to achieve localized drug delivery and improve patient compliance [].
Q13: Are there in vitro studies investigating the synergistic effects of this compound with other antibiotics?
A16: Yes, research suggests that this compound, when combined with azithromycin, exhibits synergistic and additive effects against various respiratory pathogens, including Klebsiella pneumoniae and Haemophilus influenzae []. This highlights the potential of antibiotic combinations in improving treatment efficacy and combating antibiotic resistance.
Disclaimer and Information on In-Vitro Research Products
Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.
![4-(6-Hydroxy-7-tricyclo[3.3.1.13,7]dec-1-yl-2-naphthalenyl)benzoic acid](/img/structure/B1668750.png)
![6-Cyclohexyl-3-(pyridin-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole](/img/structure/B1668763.png)
