Isoniazid
Overview
Description
Isoniazid, also known as isonicotinic acid hydrazide, is a synthetic antimicrobial agent primarily used in the treatment and prevention of tuberculosis. It was first synthesized in 1912 and introduced into clinical practice in the 1950s. This compound is a first-line antituberculosis medication due to its high efficacy and selectivity against Mycobacterium tuberculosis, the bacterium responsible for tuberculosis .
Preparation Methods
Synthetic Routes and Reaction Conditions: Isoniazid is typically synthesized through the reaction of isonicotinic acid with hydrazine hydrate. The process involves the esterification of isonicotinic acid with an alcohol and an acylation reagent to form isonicotinic acid ester. This ester is then reacted with hydrazine hydrate to produce this compound .
Industrial Production Methods: In industrial settings, the preparation of this compound involves the following steps:
Esterification: Isonicotinic acid is esterified with an alcohol (e.g., methanol) in the presence of an acid catalyst.
Hydrazinolysis: The ester is then reacted with hydrazine hydrate under controlled temperature conditions to yield this compound.
Purification: The crude product is purified through recrystallization, decolorization, and washing to achieve high purity and yield
Chemical Reactions Analysis
Types of Reactions: Isoniazid undergoes various chemical reactions, including:
Oxidation: this compound can be oxidized to form isonicotinic acid.
Reduction: It can be reduced to form hydrazine derivatives.
Substitution: this compound can participate in nucleophilic substitution reactions
Common Reagents and Conditions:
Oxidation: Potassium permanganate or hydrogen peroxide can be used as oxidizing agents.
Reduction: Sodium borohydride or lithium aluminum hydride can be used as reducing agents.
Substitution: Alkyl halides or acyl chlorides can be used for nucleophilic substitution reactions
Major Products:
Oxidation: Isonicotinic acid.
Reduction: Hydrazine derivatives.
Substitution: Various substituted isonicotinic acid derivatives
Scientific Research Applications
Tuberculosis Treatment
Primary Use
Isoniazid is a cornerstone in the treatment of all forms of tuberculosis, particularly those caused by Mycobacterium tuberculosis. It is often administered in combination with other antitubercular drugs such as rifampin and pyrazinamide to enhance efficacy and reduce the development of drug resistance. The standard regimen typically involves a daily dose of 300 mg for six months .
Mechanism of Action
this compound inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall. This action leads to bacterial cell death, making it effective in both active and latent tuberculosis infections .
Neurodegenerative Disease Research
Potential in Alzheimer's Disease
Recent studies have explored the potential of this compound in treating Alzheimer's disease. Research using APP/PS1 transgenic mouse models demonstrated that this compound administration improved cognitive performance and reduced amyloid-beta plaques, a hallmark of Alzheimer's pathology. The compound's ability to inhibit BACE1 enzymatic activity suggests a dual role in reducing plaque formation and exerting anti-inflammatory effects within the central nervous system .
| Study Focus | Findings |
|---|---|
| Cognitive Performance | Improved in APP/PS1 mice treated with this compound |
| Amyloid-Beta Plaques | Significant reduction observed |
| Mechanism | Inhibition of BACE1 and anti-inflammatory properties |
Anti-Inflammatory Applications
Inflammation Inhibition
this compound has been identified as a dual inhibitor of inflammation, showing comparable efficacy to standard anti-inflammatory drugs like ibuprofen. In vitro studies reported that certain derivatives of this compound exhibited significant anti-inflammatory activities, with IC50 values indicating potent inhibition of reactive oxygen species and urease enzyme activity .
| Compound | IC50 (µg/mL) | Activity Type |
|---|---|---|
| This compound Derivative 12 | 12.3 | Urease Inhibition |
| This compound Derivative 23 | 12.3 | Anti-Inflammatory |
Drug Delivery Systems
Nanotechnology in Drug Delivery
Innovative approaches have been developed to enhance the delivery and efficacy of this compound through nanotechnology. A study focused on synthesizing this compound-conjugated multi-wall carbon nanotubes demonstrated improved drug delivery mechanisms that could potentially reduce side effects while enhancing therapeutic outcomes against tuberculosis .
Metabolic Studies and Novel Metabolites
Identification of Novel Metabolites
Research has identified various metabolites derived from this compound that may possess antibacterial properties. Notably, 4-isonicotinoylnicotinamide has been suggested to exhibit potential antibacterial activity due to its structural similarity with active forms of this compound . Metabolomic studies have also characterized hydrazones formed during this compound metabolism, which may contribute to its antitubercular effects by interacting with metabolic pathways in Mycobacterium species .
Side Effects and Nutritional Implications
Pellagra Risk Associated with this compound
Large-scale use of this compound has been linked to nutritional deficiencies, particularly pellagra, due to its interference with niacin metabolism. A study conducted in Malawi highlighted the increased risk for pellagra among populations exposed to high doses of this compound, emphasizing the need for nutritional monitoring during treatment .
Mechanism of Action
Isoniazid is a prodrug that requires activation by the bacterial enzyme catalase-peroxidase (KatG). Once activated, it inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall. This inhibition disrupts cell wall synthesis, leading to bacterial cell death. This compound also interferes with DNA, lipid, carbohydrate, and nicotinamide adenine dinucleotide (NAD) synthesis, contributing to its bactericidal effects .
Comparison with Similar Compounds
Rifampicin: Another first-line antituberculosis drug that inhibits bacterial RNA synthesis.
Ethambutol: Inhibits the synthesis of the mycobacterial cell wall by targeting arabinosyl transferases.
Pyrazinamide: Disrupts mycobacterial cell membrane metabolism and transport functions
Uniqueness of Isoniazid: this compound’s uniqueness lies in its specific mechanism of action, targeting mycolic acid synthesis, which is crucial for the mycobacterial cell wall. Its ability to be used both as a monotherapy for latent tuberculosis and in combination with other drugs for active tuberculosis makes it a versatile and essential medication in tuberculosis treatment .
Biological Activity
Isoniazid (INH), chemically known as isonicotinic acid hydrazide, is a critical first-line antibiotic used primarily in the treatment and prevention of tuberculosis (TB). Its biological activity is characterized by its bactericidal effects against Mycobacterium tuberculosis, the causative agent of TB, and its mechanism of action involves complex biochemical interactions that inhibit bacterial cell wall synthesis.
This compound is a prodrug that requires activation by the bacterial enzyme catalase-peroxidase (KatG). Upon activation, it forms reactive species that bind to the enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in mycobacteria. This binding inhibits lipid synthesis and ultimately disrupts the integrity of the bacterial cell wall, leading to cell death .
Key Points:
- Activation : INH is activated by KatG.
- Target Enzyme : InhA, involved in fatty acid synthesis.
- Outcome : Inhibition of mycolic acid production, leading to bactericidal effects.
Biological Activity and Efficacy
The bactericidal activity of this compound has been extensively studied. In vitro studies indicate that INH can significantly increase ATP levels and enhance oxygen consumption in Mycobacterium bovis BCG, indicating a metabolic shift that supports its bactericidal action .
Table 1: Summary of this compound's Biological Activity
| Parameter | Effect |
|---|---|
| Bactericidal Activity | Effective against M. tuberculosis |
| Mechanism | Inhibits mycolic acid synthesis |
| Cellular Impact | Increases ATP production |
| Resistance Development | Common in clinical settings |
Clinical Studies and Case Reports
Numerous clinical studies have evaluated the effectiveness of this compound in various treatment regimens. A significant study compared a 9-month regimen of this compound monotherapy against a shorter combination therapy with rifampin. Results indicated that while both regimens were effective, the combination therapy was superior in preventing active TB disease among participants .
Case Study: this compound Overdose
A case reported an accidental overdose of this compound in a 68-year-old male with latent TB. The patient was managed with supportive care rather than the commonly recommended intravenous pyridoxine. This case highlights the importance of individualized treatment approaches and suggests that supportive management can be effective even in overdose scenarios .
Resistance to this compound
Resistance to this compound remains a significant challenge in TB treatment. Studies indicate that mono-resistant strains can complicate treatment outcomes, but patients with INH resistance can still respond favorably to other first-line agents .
Table 2: Resistance Patterns and Treatment Outcomes
| Resistance Type | Treatment Success Rate | Notes |
|---|---|---|
| INH Mono-resistant | 90% | Susceptible to other first-line drugs |
| Drug-susceptible | 89% | Standard treatment protocols effective |
Q & A
Q. How can researchers design experiments to evaluate Isoniazid's efficacy against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) while controlling for genetic heterogeneity in bacterial populations?
Methodological Answer:
- Experimental Design: Use a combination of minimum inhibitory concentration (MIC) assays and whole-genome sequencing to correlate resistance patterns with mutations (e.g., katG, inhA). Include isogenic strains to isolate resistance mechanisms .
- Controls: Incorporate positive (rifampicin-sensitive strains) and negative controls (non-tuberculous mycobacteria) to validate specificity.
- Data Interpretation: Apply statistical models (e.g., logistic regression) to account for genetic variability, referencing guidelines for pharmacological reproducibility .
Q. What advanced methodologies resolve contradictions in hepatotoxicity data for this compound across diverse demographic cohorts?
Methodological Answer:
- Meta-Analysis Framework: Aggregate clinical trial data using PRISMA guidelines, stratifying by variables like age, ethnicity, and NAT2 acetylator status (slow vs. fast metabolizers) .
- In Vitro/In Vivo Correlation: Use primary hepatocyte cultures from different ethnic populations to model metabolic pathways, paired with LC-MS/MS to quantify toxic metabolites (e.g., hydrazine derivatives) .
- Statistical Tools: Apply Bayesian analysis to weigh conflicting evidence, emphasizing covariates identified in preclinical models .
Q. How to optimize pharmacokinetic/pharmacodynamic (PK/PD) models for this compound in pediatric TB patients, considering developmental metabolic variations?
Methodological Answer:
- Sampling Strategy: Collect serial plasma samples across weight-adjusted dosing intervals. Use population PK modeling (e.g., NONMEM) to account for age-related clearance differences .
- Biomarker Integration: Measure acetylhydrazine levels and correlate with CYP2E1 activity assays to predict toxicity thresholds .
- Validation: Cross-validate models using pediatric data from high-TB-burden regions, adhering to ethical guidelines for pediatric research .
Q. What in vitro models best replicate the hypoxic granuloma microenvironment to test this compound's bactericidal activity?
Methodological Answer:
- Model Development: Use 3D granuloma analogs (e.g., human macrophage spheroids under 1–5% O₂) with embedded M. tuberculosis .
- Drug Penetration Assays: Quantify this compound diffusion using fluorescent analogs and confocal microscopy, referencing standardized hypoxia protocols .
- Data Presentation: Summarize results in dose-response matrices, highlighting oxygen-dependent efficacy shifts .
Q. How can genomic and transcriptomic data be systematically integrated to identify novel this compound resistance mechanisms?
Methodological Answer:
- Multi-Omics Pipeline: Combine RNA-seq (bacterial transcriptome under sub-MIC this compound) with CRISPR interference (CRISPRi) to validate gene targets .
- Bioinformatics Tools: Use PANTHER for pathway enrichment analysis and STRING for protein interaction networks, citing reproducibility standards .
- Contradiction Management: Apply Fisher’s exact test to distinguish adaptive responses from resistance mutations in longitudinal isolates .
Q. What strategies ensure methodological rigor when comparing this compound's bactericidal activity in acidic vs. neutral phagolysosomes?
Methodological Answer:
- pH-Controlled Assays: Use THP-1 macrophages with lysosomal pH modulators (e.g., bafilomycin A1). Measure intracellular bacterial load via CFU and luminescence .
- Standardization: Adopt CLSI guidelines for intracellular drug efficacy, including buffer-adjusted MICs .
- Statistical Reporting: Include error bars for pH variability and ANOVA for cross-condition comparisons .
Q. How to address discrepancies between in vitro efficacy and clinical outcomes in this compound monotherapy trials?
Methodological Answer:
- Translational Bridging: Perform hollow-fiber infection models (HFIM) mimicking human PK profiles to identify dose-dependent resistance emergence .
- Data Harmonization: Use GRADE criteria to evaluate evidence quality, emphasizing gaps in preclinical-clinical extrapolation .
- Ethical Replication: Reference IRB protocols for retrospective clinical data analysis .
Properties
IUPAC Name |
pyridine-4-carbohydrazide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
QRXWMOHMRWLFEY-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1=CN=CC=C1C(=O)NN |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C6H7N3O |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
| Record name | isoniazid | |
| Source | Wikipedia | |
| URL | https://en.wikipedia.org/wiki/Isoniazid | |
| Description | Chemical information link to Wikipedia. | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID8020755 |
Source
|
| Record name | Isoniazid | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8020755 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
137.14 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Isoniazid appears as odorless colorless or white crystals or white crystalline powder. Taste is slightly sweet at first and then bitter. pH (1% aqueous solution) 5.5-6.5. pH (5% aqueous solution) 6-8. (NTP, 1992), Solid, WHITE CRYSTALLINE ODOURLESS POWDER. |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Isoniazid | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015086 | |
| 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. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
Flash Point |
374 °F (NTP, 1992), > 250 °C |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
Solubility |
13.7 [ug/mL] (The mean of the results at pH 7.4), greater than or equal to 100 mg/mL at 77 °F (NTP, 1992), Solubility in alcohol at 25 °C: about 2, in boiling alcohol: about 10%; in chloroform: about 0.1%. Practically insoluble in ether, benzene., Sol in methyl ethyl ketone, acetone, In water, 1.4X10+5 mg/L at 25 °C, 3.49e+01 g/L, Solubility in water, g/100ml at 20 °C: 12.5 |
Source
|
| Record name | SID855769 | |
| 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 | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Isoniazid | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00951 | |
| 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 | ISONIAZID | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/1647 | |
| 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 | Isoniazid | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015086 | |
| 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. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
Vapor Pressure |
Negligible (NTP, 1992), 4.6X10-5 mm Hg at 25 °C /Estimated/ |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | ISONIAZID | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/1647 | |
| 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. | |
Mechanism of Action |
Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA., Although the mechanism of action of isoniazid is unknown, several hypotheses have been proposed. These include effects on lipids, nucleic acid biosynthesis, and glycolysis. ... /It has been suggested that/ a primary action of isoniazid /is/ to inhibit the biosynthesis of mycolic acids, important constituents of the mycobacterial cell wall. Because mycolic acids are unique to mycobacteria, this action would explain the high degree of selectivity of the antimicrobial activity of isoniazid. Exposure to isoniazid leads to a loss of acid fastness and a decrease in the quantity of methanol-extractable lipid of the microorganisms., Isoniazid is bacteriostatic for "resting" bacilli but is bactericidal for rapidly dividing microorganisms. The minimal tuberculostatic concentration is 0.025 to 0.05 ug/ml. |
Source
|
| Record name | Isoniazid | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00951 | |
| 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 | ISONIAZID | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/1647 | |
| 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 OR WHITE CRYSTALS, OR A WHITE, CRYSTALLINE POWDER, Crystals from alcohol | |
CAS No. |
54-85-3 |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Isoniazid | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=54-85-3 | |
| 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 | Isoniazid [USP:INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000054853 | |
| 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 | Isoniazid | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00951 | |
| 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 | isoniazid | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=757078 | |
| 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. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | isoniazid | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=9659 | |
| 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. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | 4-Pyridinecarboxylic acid, hydrazide | |
| 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 | Isoniazid | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8020755 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Isoniazid | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.000.195 | |
| 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 | ISONIAZID | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/V83O1VOZ8L | |
| 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 | ISONIAZID | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/1647 | |
| 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 | Isoniazid | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015086 | |
| 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. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
Melting Point |
340.5 °F (NTP, 1992), 171.4 °C, 170-173 °C |
Source
|
| Record name | ISONIAZID | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20540 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Isoniazid | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00951 | |
| 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 | ISONIAZID | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/1647 | |
| 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 | Isoniazid | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015086 | |
| 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. | |
| Record name | ISONIAZID (OBSOLETE) | |
| Source | ILO-WHO International Chemical Safety Cards (ICSCs) | |
| URL | https://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=1258 | |
| Description | The International Chemical Safety Cards (ICSCs) are data sheets intended to provide essential safety and health information on chemicals in a clear and concise way. The primary aim of the Cards is to promote the safe use of chemicals in the workplace. | |
| Explanation | Creative Commons CC BY 4.0 | |
Synthesis routes and methods I
Procedure details
Synthesis routes and methods II
Procedure details
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
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.
