| Targets |
(E)-3-Chlorocinnamaldehyde exerts its effects through its reactive aldehyde group and the alpha,beta-unsaturated carbonyl system, which is a Michael acceptor capable of forming covalent adducts with biological nucleophiles (e.g., thiols, amines). Chloro-substituted cinnamaldehyde derivatives have documented antimicrobial properties, likely due to the ability of the alpha,beta-unsaturated aldehyde to modify essential bacterial proteins/enzymes via covalent Michael addition. The compound may interact with bacterial cell membranes, causing membrane disruption. It may also inhibit class C beta-lactamase from Enterobacter cloacae 908R, with reported IC₅0 values of 4,200 nM (4.2 microM) for certain derivatives, suggesting potential synergy with beta-lactam antibiotics.
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|---|---|
| ln Vitro |
(E)-3-Chlorocinnamaldehyde is a research intermediate rather than a drug, so detailed in vitro biological activity data is limited. For chloro-substituted cinnamaldehyde derivatives, in vitro antibacterial activity has been reported against Staphylococcus aureus ATCC25923, with MIC values below 1 microg/mL for some compounds, over 256-fold better than reference drugs. Cinnamaldehyde and its derivatives inhibit bacterial growth in a dose-dependent manner, with the MIC of cinnamaldehyde comparable to o-phthalaldehyde and sodium hypochlorite, and lower than hydrogen peroxide and lactic acid. The effect of substituted cinnamates on bacterial growth is more evident against Gram-negative bacteria. As an alpha,beta-unsaturated aldehyde, (E)-3-Chlorocinnamaldehyde likely exhibits alkylating activity toward biological thiols (e.g., glutathione), which may contribute to antimicrobial activity and cellular stress responses. The compound may be metabolized by aldehyde dehydrogenase (ALDH) and glutathione S-transferase (GST) enzymes.
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| ln Vivo |
No direct in vivo activity data for (E)-3-Chlorocinnamaldehyde is available, as it is primarily an organic synthesis intermediate. In vivo studies on cinnamaldehyde and its derivatives in animal models show antimicrobial activity, anti-inflammatory effects, and metabolic effects. For example, cinnamaldehyde (100-200 mg/kg oral) in rodent models has been shown to reduce blood glucose levels, improve insulin sensitivity, reduce inflammation in colitis models, and reduce bacterial load in infection models. For (E)-3-Chlorocinnamaldehyde, similar in vivo efficacy would be expected at comparable doses (50-200 mg/kg oral or IP), depending on the extent of metabolic conjugation and clearance.
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| Enzyme Assay |
Class C beta-lactamase inhibition assay: Purified class C beta-lactamase from Enterobacter cloacae 908R is incubated in 50 mM phosphate buffer (pH 7.0) containing 100 microM nitrocefin (chromogenic cephalosporin substrate) and varying concentrations of (E)-3-Chlorocinnamaldehyde (0.1-1000 microM) at 25degC. Hydrolysis of nitrocefin is monitored by measuring the increase in absorbance at 490 nm over 5-10 minutes. The initial velocity (Vo) is calculated from the linear portion of the progress curve. The IC₅0 (concentration causing 50% inhibition of beta-lactamase activity) is calculated from a dose-response curve by comparing the initial velocities of compound-treated samples to a control (no inhibitor). For related cinnamaldehyde derivatives, IC₅0 values of approximately 4,200 nM (4.2 microM) have been reported.
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| Cell Assay |
Antibacterial susceptibility testing (broth microdilution) for (E)-3-Chlorocinnamaldehyde: Bacterial strains (e.g., Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) are cultured in Mueller-Hinton broth overnight at 37degC. The bacterial suspension is adjusted to 0.5 McFarland standard (~1 × 10⁸ CFU/mL) and diluted to ~5 × 10⁵ CFU/mL. (E)-3-Chlorocinnamaldehyde is dissolved in DMSO (≤1% final concentration) and serially diluted two-fold in 96-well plates to final concentrations of 0.5-512 microg/mL. The bacterial suspension (100 microL) is added to each well. Plates are incubated at 37degC for 18-24 hours. The MIC (minimum inhibitory concentration) is determined as the lowest concentration with no visible bacterial growth. For S. aureus, chloro-substituted cinnamaldehyde derivatives can have MIC values below 1 microg/mL. The MBC (minimum bactericidal concentration) is determined by subculturing 10 microL from wells with no visible growth onto Mueller-Hinton agar plates and incubating at 37degC for 24 hours. The MBC is the lowest concentration that kills ≥99.9% of the initial inoculum.
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| Animal Protocol |
Biofilm inhibition assay for (E)-3-Chlorocinnamaldehyde: Staphylococcus aureus or Pseudomonas aeruginosa is cultured in tryptic soy broth (TSB) supplemented with 0.25-0.5% glucose overnight at 37degC. The culture is diluted 1:100 in fresh TSB, and 200 microL is dispensed into 96-well polystyrene plates. (E)-3-Chlorocinnamaldehyde is added at sub-MIC concentrations (e.g., 0.1-50 microg/mL). Plates are incubated at 37degC for 24-48 hours to allow biofilm formation. Planktonic cells are removed by gentle washing with PBS three times. Adherent biofilm cells are fixed with 100% methanol for 15 minutes, then stained with 0.1% crystal violet solution for 20 minutes. Excess stain is removed by washing with water, and bound crystal violet is solubilized with 33% glacial acetic acid. Absorbance is measured at 595 nm. Biofilm formation is expressed as a percentage of control (untreated wells). CLSM with LIVE/DEAD staining (SYTO 9 and propidium iodide) can be used to visualize biofilm architecture and viability.
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| ADME/Pharmacokinetics |
For (E)-3-Chlorocinnamaldehyde as an intermediate, specific pharmacokinetic data is not available. As a low-molecular-weight (166.6 g/mol) alpha,beta-unsaturated aldehyde, it is expected to be rapidly absorbed following oral administration. Metabolism is likely primarily by aldehyde dehydrogenase (ALDH) in the liver, converting the aldehyde group to the corresponding carboxylic acid (3-chlorocinnamic acid), followed by further Phase II conjugation (glucuronidation, glycine conjugation). Reduction by aldo-keto reductases (AKRs) may produce the corresponding alcohol (3-chlorocinnamyl alcohol). The alpha,beta-unsaturated system can undergo Michael addition with glutathione (GSH) via GST-catalyzed conjugation, leading to GSH adducts that are excreted in bile. Plasma elimination half-life is expected to be short (1-4 hours). For cinnamaldehyde in rats, oral bioavailability is low (<20%) due to extensive first-pass metabolism. Cinnamaldehyde is rapidly converted to cinnamic acid, which is further metabolized to benzoic acid and then hippuric acid (glycine conjugate), excreted in urine. For research applications, the compound is typically used in vitro at concentrations of 0.1-100 microg/mL, and in vivo at doses of 10-200 mg/kg oral or IP in animal models.
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| Toxicity/Toxicokinetics |
For (E)-3-Chlorocinnamaldehyde, GHS hazard information: Signal word: Warning. Hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing). As a reactive alpha,beta-unsaturated aldehyde, the compound may be a skin sensitizer (contact dermatitis) and may cause respiratory sensitization. The compound is flammable (flash point not specified). Standard safety precautions: Use in well-ventilated areas (fume hood), wear gloves (nitrile), lab coat, and safety goggles, avoid inhalation and skin contact. Store at -20degC (General tips) in a tightly closed container, protected from light.
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| References | |
| Additional Infomation |
(E)-3-Chlorocinnamaldehyde (CAS#56578-37-1) is a research-grade organic compound used as an intermediate in organic synthesis for the construction of heterocyclic frameworks (e.g., pyrazoles, isoxazoles, pyrimidines, quinolines). The alpha,beta-unsaturated aldehyde system participates in Michael additions, Knoevenagel condensations, and cross-coupling reactions (Suzuki, Heck, Sonogashira). This compound is also used as a fragrance and flavoring agent. Chloro-substituted cinnamaldehydes have documented antimicrobial properties. (E)-3-Chlorocinnamaldehyde is not an FDA-approved drug; it is for research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C9H7CLO
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|---|---|
| Molecular Weight |
166.60
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| Exact Mass |
166.019
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| CAS # |
56578-37-1
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| PubChem CID |
5706768
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
11
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| Complexity |
154
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)Cl)/C=C/C=O
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| InChi Key |
GTQLBYROWRZDHS-DUXPYHPUSA-N
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| InChi Code |
InChI=1S/C9H7ClO/c10-9-5-1-3-8(7-9)4-2-6-11/h1-7H/b4-2+
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| Chemical Name |
(E)-3-(3-chlorophenyl)prop-2-enal
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| Synonyms |
(E)-m-Chlorocinnamaldehyde
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.0024 mL | 30.0120 mL | 60.0240 mL | |
| 5 mM | 1.2005 mL | 6.0024 mL | 12.0048 mL | |
| 10 mM | 0.6002 mL | 3.0012 mL | 6.0024 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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