Carbazole targets DNA, forming a minor groove complex that suppresses DNA or RNA synthesis. This interaction with DNA suggests potential as an antiproliferative agent. Carbazole derivatives have been shown to exhibit antibacterial and antifungal activities, targeting microbial pathogens. The carbazole scaffold is also a motif in pharmaceuticals such as carvedilol.

Carbazole demonstrates in vitro activity by forming a DNA minor groove complex, which suppresses the synthesis of new DNA or RNA. Some carbazole derivatives exhibit antibacterial and antifungal activities. The compound is used as an intermediate in the synthesis of pharmaceuticals, agrochemicals, dyes, and pigments.

In vivo activity of carbazole has been suggested by its use as a pharmaceutical intermediate in drugs such as carvedilol, which is used to treat high blood pressure and prevent cardiac arrhythmias. The compound itself is not a therapeutic agent, but its derivatives have demonstrated various pharmacological activities.

Carbazole's interaction with DNA can be assessed using in vitro assays such as DNA binding studies, which measure the compound's affinity for DNA and its ability to intercalate or form minor groove complexes. These assays typically use spectroscopic techniques such as UV-Vis absorption, fluorescence, or circular dichroism to monitor DNA-compound interactions.

In vitro cellular assays for carbazole are not typically performed on the parent compound, as it is primarily used as a synthetic intermediate. However, carbazole derivatives are evaluated for antibacterial and antifungal activities using standard microbial growth inhibition assays. Antiproliferative activity can be assessed using cancer cell lines.

In vivo animal experiments for carbazole are not extensively documented, as the compound is primarily used as a synthetic intermediate. Its derivatives, such as carvedilol, have been extensively studied in animal models for cardiovascular indications.

Metabolism / Metabolites
Spotted trout (Salvelinus fontinalis) were orally exposed to a variety of polycyclic aromatic hydrocarbons (PACs), including benzo[a]pyrene, carbazole, chloroquine, dibenzofuran, dibenzothiophene, fluorene, phenanthrene, and pyrene. Fish were euthanized 7 days after exposure, and the gallbladders were removed for bile analysis. The presence of PAC derivatives in bile was determined using high-performance liquid chromatography (HPLC) combined with fluorescence (F) and ultraviolet (UV) detection without pretreatment. Glucuronide conjugates were dominant in all exposure groups, while the content of phenolic compounds and starting materials varied (0-53%). Compound identification was confirmed by selective extraction of less polar unconjugated PACs and enzymatic hydrolysis of water-soluble substances. Subsequently, the generated phenolic compounds were characterized by HPLC and/or gas chromatography-mass spectrometry (GC-MS). The total metabolite levels varied considerably among different compounds. Nitrogen-containing heterocyclic compounds, especially carbazole, quinolones, and pyridine, are common environmental pollutants. Carbazole is toxic to organisms, but our understanding of its persistence and biotransformation processes in ecosystems remains incomplete. The detoxification capabilities of microorganisms for harmful exogenous substances are receiving increasing attention. This study evaluated the ability of three filamentous fungi (belonging to the genus Cunninghamella) to remove carbazole. Cunninghamella elegans IM 1785/21Gp and Cunninghamella echinulata IM 2611 strains effectively removed carbazole. After 120 hours of incubation, strains IM 1785/21Gp and IM 2611 converted 93% and 82% of the exogenous substance, respectively, at an initial concentration of 200 mg L⁻¹. 2-Hydroxycarbazole was identified for the first time as a carbazole metabolite produced by the filamentous fungus Cunninghamella. The extracts did not show increased toxicity to Artemia franciscana after incubation. Furthermore, we found that carbazole affects the phospholipid composition of the tested filamentous fungal cells, indicating its detrimental effect on the fungal cell membrane. The phospholipid level change was most significant in strain IM 1785/21Gp after carbazole was added to culturate the filamentous fungi. Four bacterial strains isolated from hydrocarbon-contaminated soil in Lagos, Nigeria, exhibited extensive degradation capabilities for carbazole (an N-heterocyclic aromatic hydrocarbon). Physicochemical analysis of the sampling sites (ACPP, MWO, NESU) showed that these soils were severely contaminated, with high hydrocarbon content (157,067.9 mg/kg) and heavy metal content. Phylogenetic analysis of these four strains identified them as Achromobacter sp. SL1, Pseudomonas sp. SL4, Microbacterium esteraromaticum SL6, and Stenotrophomonas maltophilia BA, respectively. During the 30-day culture period, the degradation rates of carbazole by the four isolated strains were as follows: SL1 strain 0.057 mg L⁻¹ h⁻¹, SL4 strain 0.062 mg L⁻¹ h⁻¹, SL6 strain 0.036 mg L⁻¹ h⁻¹, and BA strain 0.050 mg L⁻¹ h⁻¹. Gas chromatography (GC) analysis showed that after 30 days of culture, strains SL1, SL4, SL6, and BA degraded 81.3%, 85%, 64.4%, and 76% of 50 mg L⁻¹ carbazole, respectively. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) analyses of extracts from growing and dormant cells of strains SL1, SL4, and SL6 cultured on carbazole medium revealed the detection of anthranilic acid and catechol, while these metabolites were not detected in strain BA under the same conditions. This study is the first to demonstrate that African isolates can undergo angular dioxygenation and mineralization of carbazole. 3-Hydroxycarbazole is reportedly a metabolite of carbazole in rat and rabbit urine.

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Pharmacokinetic data for carbazole are not typically characterized, as it is a synthetic intermediate rather than a therapeutic agent. Its physicochemical properties, such as its aromatic structure and lipophilicity, would influence its absorption and distribution if administered systemically.

Toxicity Summary
Identification and Uses: Carbazole is a solid. It is found in the incomplete combustion products of nitrogen-containing organics (such as tobacco). It is an important dye intermediate. It is also used in the manufacture of UV-sensitive photographic films and as a reagent for lignin, carbohydrates, and formaldehyde. Carbazole, when modified, exhibits a wide range of biological activities, including antibacterial, antimalarial, anticancer, and anti-Alzheimer's properties. Human Exposure and Toxicity: No relevant data are available. Animal Studies: Fifty male and fifty female mice (6 weeks old) were divided into groups and fed pelleted diets containing 0.6%, 0.3%, or 0.15% industrial-grade carbazole, or no treatment (control group). This treatment lasted for 96 weeks; subsequently, the animals were fed a basal diet until sacrifice at week 104. Neoplastic lesions were found in the liver and forestomach. The lesions in the liver were classified as neoplastic nodules and hepatocellular carcinoma. The incidence of both lesions in the livers of all carbazole-fed groups was significantly higher than in the control group. In rats, no maternal or developmental toxicity was observed after transdermal administration of carbazole at doses of 2.5, 25.0, and 250.0 mg/kg. In the Ames assay, carbazole was not mutagenic, regardless of metabolic activation. Intraperitoneal injection of carbazole had a moderate chromosomal breakage effect in mice. It induced dominant slant sperm length and sperm head abnormalities in male mice.

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Interactions
A group of 40 six-week-old Syrian golden hamsters (sex unspecified) were intraperitoneally injected with 20 mg/kg body weight of 2,2'-dioxo-N-nitrosodipropylamine (DOPN), while another group of 80 animals received no treatment. One week later, half of each group continued to be fed a basal diet, while the other half were fed a basal diet containing 0.2% carbazole until sacrifice at week 40. The number of GST-P positive lesions (expressed as lesions/cm²) were as follows: basal diet group, 0; carbazole diet group, 3.6±1.3 (p<0.001); DOPN + basal diet group, 9.2±4.1; DOPN + carbazole diet group, 19.0 ± 7.6 (p < 0.001). Tobacco and coffee contain various compounds, including azoles, but information on the reproductive and teratogenic effects of these compounds is scarce. This study investigated the effects of certain azoles, alone or in combination with ethanol, on embryonic development. Rat embryos on day 9.5 of gestation were cultured for 48 hours alone or in combination with different doses of azole compounds (benzothiazole and carbazole (BZT and CBZ, 10⁻⁶–10⁻⁴ M), 2-aminobenzothiazole (ABT, 10⁻⁴–5 × 10⁻⁴ M), thiazole (THZ, 10⁻⁸–10⁻⁴ M), and 2,5-dimethylbenzoxazole (DMBZ, 10⁻⁶–10⁻³ M)). Embryonic morphological changes were observed and scored using the Van Maele-Fabry method to assess embryonic development. Total protein and DNA content of the embryos were also measured. The results showed that BZT, THZ, and DMBZ inhibited the development of the ear and optic nerve. THZ and ABT inhibited the development of the yolk sac circulatory system and reduced the yolk sac diameter and head length. THZ, CBZ, and DMBZ inhibit brain development. All compounds resulted in significantly reduced overall scores and abnormal tail development. Ethanol also caused developmental toxicity to the heart, brain, optic and auricular systems, and mandibular processes. Except for THZ, the embryotoxicity of azole compounds in combination with ethanol was far greater than that of either chemical alone. These data suggest that some azole compounds present in tobacco and/or coffee aromas may be embryotoxic, and that the addition of ethanol enhances their toxicity to cultured rat embryos. This study investigated the photoinduced toxicity and toxicokinetics of acute exposure to specific polycyclic aromatic hydrocarbons (PAHs) in zebrafish. The photoenhanced toxicity resulting from co-exposure to ultraviolet (UV) radiation with PAHs allowed toxic effects to be observed even at PAH concentrations several orders of magnitude lower than those observed without UV exposure. Since PAHs in the environment are often present in complex mixtures, this study investigated the phototoxicity of single compounds and mixtures. In sensitive juvenile zebrafish, we determined the acute phototoxic median lethal concentration (LC50) of four PAHs (anthracite, pyrene, carbazole, and phenanthrene) to verify the hypothesis that the phototoxic pathways (anthracite and pyrene) and non-phototoxic pathways (carbazole and phenanthrene) of a mixture could be predicted based on single exposure. As predicted, anthracene and pyrene exhibited phototoxicity; however, carbazole showed moderate phototoxicity, while phenanthrene showed weak phototoxicity. The individual toxicity of each chemical was determined separately, and the toxicity of binary, ternary, and quaternary mixtures of these polycyclic aromatic hydrocarbons (PAHs) was compared to establish a predictive model for environmental mixtures. The results showed that under phototoxic conditions, the acute toxicity of PAH mixtures had an additive effect regardless of the magnitude of the photoenhancing effect. Based on the concentration of PAHs in water and the high dose of ultraviolet radiation to aquatic systems, aquatic organisms face a potential phototoxic risk.

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Non-human toxicity values
Mouse intraperitoneal injection LD50: 200 mg/kg
Rat oral LD50: >5000 mg/kg

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Toxicological data for carbazole indicate that it is a skin irritant and may cause photosensitivity. While carbazole itself is not listed as a carcinogen, some of its derivatives have shown carcinogenic effects in animal studies. Standard laboratory safety precautions should be followed when handling this compound.

[1]. A new type of DNA minor-groove complex: carbazole dication-DNA interactions. Biochemistry. 1997 Dec 9;36(49):15315-25.

[2]. carbazole and its derivatives as antitumor agents. Anticancer Agents Med Chem. 2015;15(8):1049-65.

[3]. Effect of conjugation and aromaticity of 3,6 di-substituted carbazoles on triplet energy and the implication of triplet energy in multiple-cyclic aromatic compounds. RSC Adv., 2018, 8, 9850-9857.

According to the U.S. Environmental Protection Agency (EPA), carbazole may be carcinogenic. Carbazole is a white crystal, flake, flaky, or light brown powder that readily sublimates. Under ultraviolet light, it emits strong fluorescence and long phosphorescence. (NTP, 1992) 9H-carbazole is a carbazole compound and is a tautomer of 3H-carbazole, 1H-carbazole, 8aH-carbazole, and 4aH-carbazole. Carbazole has been reported to be found in Glycosmis pentaphylla, Streptomyces, and other organisms with relevant data.

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Therapeutic Uses
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that includes publicly and privately funded human clinical studies worldwide. This website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov provides a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure being investigated); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field) from the National Library of Medicine (NLM). Carbazole is included in the database. Chemotherapy drugs used to treat cancer can have pleiotropic effects, such as directly interfering with DNA metabolism or endoplasmic reticulum function. In recent years, the use of molecularly targeted therapies as alternative cancer treatments has been on the rise due to the need to overcome adverse side effects or the emergence of drug resistance. Therefore, a major challenge is to design and synthesize novel drugs that can interact with specific cellular components (such as telomerase, topoisomerase, or protein kinase, which are frequently overexpressed or altered in cancer cells) and have low toxicity at effective doses. The main molecular targets for novel anticancer drug development include cell surface receptors, signal transduction pathways, enzymes, gene transcription, ubiquitin-proteasome/heat shock proteins, and anti-angiogenic factors. Researchers have screened for natural or synthetic polycyclic molecules with a carbazole core that exhibit good drug-like properties, aiming to enhance their bioactivity and specificity to obtain cytotoxic drugs effective against various cancer cell lines. Researchers evaluated the cytotoxicity of these compounds using various in vitro experiments (e.g., MTT assay, clonogenic assay, and flow cytometry), showing that some compounds exhibited remarkable activity at sub-micromolar concentrations. The efficacy of some carbazole derivatives has been confirmed in preclinical studies. /Carbazole Derivatives/
Throughout human evolution, the importance of natural products in the pharmaceutical and health fields has become increasingly prominent, and they continue to be an important source of novel anticancer drugs, lead compounds, and new chemical entities. Among natural products, tricyclic heteroaromatic alkaloids (such as carbazole) are an important class of natural and semi-synthetic organic compounds. In recent decades, the medicinal value of natural and semi-synthetic carbazoles has significantly increased, especially as an important class of heterocyclic antitumor drugs. Several carbazoles showing potential anticancer activity have entered clinical trials. However, due to multidrug resistance issues encountered in clinical trials, only a very small number of selected carbazoles have ultimately been approved for cancer treatment. Planar, polycyclic, and aromatic carbazoles exert their anticancer activity through DNA intercalation. Furthermore, many carbazole compounds exert cytotoxicity by inhibiting DNA-dependent enzymes such as telomerase and topoisomerase I/II. /Carbazole Derivatives/
/Exploring Therapies/ Neural stem cells are pluripotent and self-renewing cells capable of differentiating into new neurons, showing great potential in the treatment of various neurological diseases, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecule compounds capable of inducing neurogenesis and neuroprotection are not only therapeutically significant but also provide valuable tools for studying the mechanisms of neurogenesis, thus possessing particular value. In this report, we developed and screened 25 aminopropylcarbazole derivatives that enhance neurogenesis in cultured neural stem cells. Among these analogues, compound 9 exhibited excellent pro-neurogenesis and neuroprotective activity without significant toxicity. We believe compound 9 can serve as an excellent lead compound for developing various analogues and studying the potential mechanisms of neurogenesis. /Carbazole Derivatives/
/Exploring Therapies/ Trypanosoma brucei is a protozoan parasite that causes fatal human trypanosomiasis (HAT). Current standard drugs for treating HAT have many limitations, thus there is an urgent need to find novel compounds that can effectively combat trypanosoma infection. We used a \"drug repositioning\" strategy to test the anti-trypanosoma activity of the carbazole derivative \"Curaxins\". In vitro screening of 26 compounds revealed that 22 of them had nanomolar activity against sterile cultured bloodstream trypanosoma. In a mouse model of HAT, oral administration of compound 1 cured the disease. These studies confirm that compound 1 is a lead compound for developing HAT drugs. Pharmacological time-course studies showed that the main action of compound 1 is to inhibit mitosis and abnormally induce S-phase cells to enter the cell cycle. This resulted in ploid trypanosomas with 8c DNA per nucleus and three to four kinematic bodies. The effects of compound 1 on trypanosomes are similar to the \"mitotic slip\" or internal replication observed in some other eukaryotes. /Carbazole derivatives/

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Carbazole (CAS#: 86-74-8) has the molecular formula C12H9N and a molecular weight of 167.21 g/mol. It is a tricyclic aromatic heterocycle used as a pharmaceutical intermediate and in organic electronics. Some carbazole derivatives show antibacterial and antifungal activities.

167.073

86-74-8

Carbazole-d8;38537-24-5

6854

Crystals from alcohol, benzene, toluene, glacial acetic acid
White crystals
White crystals, plates, leaflets or light tan powder

1.1

355.0±11.0 °C at 760 mmHg

243-246 °C(lit.)

220 ºC

0.0±0.8 mmHg at 25°C

1.768

3.72

1

0

0

13

170

0

C1C=C2NC3C(C2=CC=1)=CC=CC=3

UJOBWOGCFQCDNV-UHFFFAOYSA-N

InChI=1S/C12H9N/c1-3-7-11-9(5-1)10-6-2-4-8-12(10)13-11/h1-8,13H

9H-carbazole

Carbazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 250 mg/mL (~1495.1 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)