Clindamycin
Descripción general
Descripción
Clindamicina es un antibiótico lincosamida utilizado para tratar una variedad de infecciones bacterianas. Es particularmente eficaz contra bacterias anaeróbicas y ciertas bacterias grampositivas, incluidas estafilococos y estreptococos. La clindamicina se utiliza comúnmente para tratar infecciones como osteomielitis, enfermedad inflamatoria pélvica, faringitis estreptocócica, neumonía e infecciones de la piel . Está disponible en varias formas, incluidas cápsulas orales, cremas tópicas y soluciones intravenosas .
Métodos De Preparación
La clindamicina se sintetiza a partir de la lincomicina, un antibiótico natural. La síntesis implica la cloración de la lincomicina para reemplazar el grupo hidroxilo en la posición 7 con un átomo de cloro . El proceso incluye varios pasos:
Aplicación del grupo protector de silicio: La lincomicina se protege primero utilizando un grupo de silicio.
Desprotección selectiva: La lincomicina protegida se somete a una desprotección selectiva.
Reacción de sustitución de Mitsunobu: La lincomicina desprotegida se somete a una reacción de sustitución de Mitsunobu.
Reacción de hidrólisis: El producto luego se hidroliza para obtener 7-epime lincomicina.
Reacción de cloración: Finalmente, la 7-epime lincomicina se clora para producir clindamicina.
La producción industrial de clorhidrato de clindamicina implica pasos de cloración, hidrólisis, extracción y concentración para obtener la forma alcalina libre, seguida de la formación de sal y dealcoholización para producir clorhidrato de clindamicina .
Análisis De Reacciones Químicas
La clindamicina se somete a diversas reacciones químicas, que incluyen:
Oxidación: La clindamicina puede oxidarse para formar sulfóxido y metabolitos N-desmetilados.
Reducción: Las reacciones de reducción son menos comunes pero pueden ocurrir en condiciones específicas.
Sustitución: La reacción de sustitución de Mitsunobu es un paso clave en su síntesis.
Los reactivos comunes utilizados en estas reacciones incluyen agentes clorantes, agentes oxidantes y agentes reductores. Los principales productos formados a partir de estas reacciones son el clorhidrato de clindamicina y sus metabolitos .
Aplicaciones Científicas De Investigación
La clindamicina tiene una amplia gama de aplicaciones de investigación científica:
Química: Se utiliza como compuesto modelo en el estudio de la síntesis y modificación de antibióticos.
Biología: La clindamicina se utiliza para estudiar la síntesis de proteínas bacterianas y los mecanismos de resistencia.
Medicina: Se utiliza ampliamente para tratar infecciones bacterianas, incluidas las causadas por Staphylococcus aureus resistente a la meticilina (MRSA) y bacterias anaeróbicas
Mecanismo De Acción
La clindamicina funciona uniéndose a la subunidad ribosómica 50S de las bacterias, inhibiendo la síntesis de proteínas. Esta acción previene la elongación de la cadena peptídica durante la traducción, deteniendo eficazmente el crecimiento bacteriano . La clindamicina se dirige al ribosoma bacteriano, interrumpiendo la reacción de transpeptidación e inhibiendo la elongación temprana de la cadena .
Comparación Con Compuestos Similares
La clindamicina se compara a menudo con otros antibióticos, como:
Lincomicina: La clindamicina es un derivado clorado de la lincomicina con propiedades mejoradas.
Amoxicilina: Un antibiótico de tipo penicilina utilizado para infecciones similares pero con un mecanismo de acción diferente.
Doxiciclina: Un antibiótico de tetraciclina con un espectro de actividad más amplio
La clindamicina es única debido a su alta eficacia contra las bacterias anaeróbicas y su capacidad para penetrar en los huesos y los abscesos, lo que la hace particularmente útil para tratar la osteomielitis y otras infecciones profundas .
Actividad Biológica
Clindamycin is an antibiotic belonging to the lincosamide class, primarily effective against anaerobic bacteria and certain protozoa. It is widely used in clinical settings for treating various infections, including skin and soft tissue infections, respiratory tract infections, and certain types of bone infections. This article delves into the biological activity of this compound, supported by data tables, case studies, and relevant research findings.
This compound exerts its antibacterial effects by inhibiting bacterial protein synthesis. It binds to the 50S ribosomal subunit of susceptible bacteria, thereby blocking peptide bond formation during translation. This mechanism is similar to that of macrolides but differs in its binding site preference, making this compound effective against a range of Gram-positive cocci and anaerobic bacteria.
Key Points:
- Target : 50S ribosomal subunit.
- Effect : Inhibition of protein synthesis.
- Spectrum : Effective against anaerobes and some protozoa.
Clinical Applications
This compound is indicated for various infections, particularly those caused by anaerobic bacteria. Its effectiveness is highlighted in several case studies:
Case Study Highlights:
- Skin and Soft Tissue Infections : this compound has shown significant efficacy in treating cellulitis and abscesses caused by Staphylococcus aureus, including methicillin-resistant strains (MRSA).
- Bone Infections : In osteomyelitis cases, this compound demonstrated favorable outcomes when combined with surgical intervention.
- Periodontal Disease : A study indicated that this compound could improve glycemic control in diabetic patients with periodontal disease, showing a mean reduction in HbA1c levels .
Efficacy Against Specific Pathogens
This compound's activity against various pathogens can be summarized in the following table:
Resistance Patterns
Resistance to this compound can occur through various mechanisms, including:
- Methylation of adenine residues in the 23S rRNA, which alters the binding site.
- Efflux pumps that expel the antibiotic from bacterial cells.
Monitoring resistance patterns is crucial, especially in hospital settings where resistant strains may emerge.
Adverse Effects and Considerations
While this compound is generally well-tolerated, it can lead to side effects such as gastrointestinal disturbances and a risk of C. difficile-associated diarrhea. The incidence of C. difficile infection has been noted to increase with this compound use, necessitating careful patient monitoring .
Important Considerations:
- Caution in prescribing for patients with a history of gastrointestinal disorders.
- Monitoring for signs of C. difficile infection during treatment.
Q & A
Basic Research Questions
Q. How can researchers design bioequivalence trials for generic clindamycin formulations, and what statistical criteria ensure validity?
- Methodological Answer : Bioequivalence studies should follow CHMP guidelines, using a randomized, crossover design with 90% confidence intervals for AUC0-inf and Cmax within 0.8–1.24. Linear pharmacokinetics (150–600 mg dose range) justify dose selection (e.g., 300 mg). Analytical methods (e.g., HPLC) and adherence to EMEA/CHMP/EWP/40326/2006 ensure reproducibility .
Q. What experimental methods are recommended to detect inducible this compound resistance in Staphylococcus aureus?
- Methodological Answer : Use the D-zone test: place erythromycin (15 µg) and this compound (2 µg) discs 15 mm apart on Mueller-Hinton agar. Flattening of the this compound inhibition zone near erythromycin indicates inducible resistance. Confirm with CLSI M100 standards and statistical tools (e.g., SPSS) for data analysis .
Q. How should systematic reviews assess this compound’s efficacy in preventing post-surgical infections?
- Methodological Answer : Employ PRISMA guidelines, extract data from RCTs using tools like the Cochrane Risk of Bias Tool (e.g., randomization, blinding). Pool data via meta-analysis (fixed/random effects models) and address heterogeneity with sensitivity analysis. Focus on outcomes like infection rates in third molar extractions .
Q. What are key considerations for designing in vitro susceptibility testing of this compound against drug-resistant Staphylococci?
- Methodological Answer : Use microdilution methods to determine MICs, adhering to CLSI-M100 standards. Include positive controls (e.g., ciprofloxacin) and analyze data with Fisher’s exact test to compare sensitivity across strains. Account for regional resistance patterns in study design .
Advanced Research Questions
Q. How can physiologically based pharmacokinetic (PBPK) models optimize this compound dosing in pediatric populations?
- Methodological Answer : Develop PBPK models using adult PK data (extracted via Plot Digitizer®) and scale parameters (e.g., organ weights, enzyme expression) using ontogeny functions. Validate with opportunistic pediatric data and software like Simcyp®. Address variability in CYP3A4 maturation .
Q. What molecular dynamics (MD) approaches elucidate this compound resistance mechanisms in bacterial ribosomes?
- Methodological Answer : Simulate this compound binding to wild-type (WT) and mutant (A2058G) 23S rRNA ribosome fragments in explicit solvent. Analyze conformational flexibility (RMSD, RMSF) and stacking interactions (e.g., G2505-U2506) using GROMACS/AMBER. Correlate findings with in vitro resistance data .
Q. How can factorial design optimize this compound-loaded nanogel formulations for enhanced delivery?
- Methodological Answer : Apply 3<sup>2</sup> full factorial design to evaluate independent variables (e.g., polymer concentration, cross-linker ratio). Use DOE software to analyze responses (entrapment efficiency, release kinetics). Validate with in vitro characterization (e.g., TEM, DSC) .
Q. What pharmacovigilance strategies address this compound-associated C. difficile colitis in clinical trials?
- Methodological Answer : Monitor diarrhea incidence (>20% systemic cases) and confirm pseudomembranous colitis via toxin PCR. Exclude high-risk patients (e.g., prior C. difficile history) and analyze covariates (e.g., age, concomitant antibiotics) using logistic regression .
Q. How do cross-resistance patterns between this compound and macrolides inform combination therapy design?
- Methodological Answer : Test for erm/mef resistance genes via PCR in isolates with MLSB phenotypes. Use checkerboard assays to quantify synergism (FIC index ≤0.5) with erythromycin. Model PK/PD interactions (e.g., AUC/MIC) to optimize dosing .
Q. What statistical methods resolve contradictions in this compound’s efficacy for bacterial vaginosis trials?
Propiedades
IUPAC Name |
(2S,4R)-N-[(1S,2S)-2-chloro-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C18H33ClN2O5S/c1-5-6-10-7-11(21(3)8-10)17(25)20-12(9(2)19)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,22-24H,5-8H2,1-4H3,(H,20,25)/t9-,10+,11-,12+,13-,14+,15+,16+,18+/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
KDLRVYVGXIQJDK-AWPVFWJPSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCCC1CC(N(C1)C)C(=O)NC(C2C(C(C(C(O2)SC)O)O)O)C(C)Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CCC[C@@H]1C[C@H](N(C1)C)C(=O)N[C@@H]([C@@H]2[C@@H]([C@@H]([C@H]([C@H](O2)SC)O)O)O)[C@H](C)Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C18H33ClN2O5S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
21462-39-5 (mono-hydrochloride), 58207-19-5 (mono-HCl, mono-hydrate) |
Source
|
| Record name | Clindamycin [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0018323449 | |
| 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 |
DTXSID2022836 |
Source
|
| Record name | Clindamycin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2022836 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
425.0 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Mechanism of Action |
Clindamycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Clindamycin palmitate hydrochloride and clindamycin phosphate are inactive until hydrolyzed to free clindamycin. This hydrolysis occurs rapidly in vivo. Clindamycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of erythromycin, chloramphenicol, and lincomycin., Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis., ... Clindamycin is not a substrate for macrolide efflux pumps, and strains that are resistant to macrolides by this mechanism are susceptible to clindamycin. |
Source
|
| Record name | CLINDAMYCIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3037 | |
| 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 |
Yellow, amorphous solid | |
CAS No. |
18323-44-9 |
Source
|
| Record name | Clindamycin | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=18323-44-9 | |
| 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 | Clindamycin [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0018323449 | |
| 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 | Clindamycin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2022836 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Clindamycin | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.038.357 | |
| 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 | CLINDAMYCIN | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/3U02EL437C | |
| 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 | CLINDAMYCIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3037 | |
| 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
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
Descargo de responsabilidad e información sobre productos de investigación in vitro
Tenga en cuenta que todos los artículos e información de productos presentados en BenchChem están destinados únicamente con fines informativos. Los productos disponibles para la compra en BenchChem están diseñados específicamente para estudios in vitro, que se realizan fuera de organismos vivos. Los estudios in vitro, derivados del término latino "in vidrio", involucran experimentos realizados en entornos de laboratorio controlados utilizando células o tejidos. Es importante tener en cuenta que estos productos no se clasifican como medicamentos y no han recibido la aprobación de la FDA para la prevención, tratamiento o cura de ninguna condición médica, dolencia o enfermedad. Debemos enfatizar que cualquier forma de introducción corporal de estos productos en humanos o animales está estrictamente prohibida por ley. Es esencial adherirse a estas pautas para garantizar el cumplimiento de los estándares legales y éticos en la investigación y experimentación.
