13220-57-0

Basic information

• Product Name: TRYPTANTHRIN
• Synonyms: TRYPTANTHRIN;INDOLO[2,1-B]QUINAZOLINE-6,12-DIONE;tryptanthrine;6,12-Dihydroindolo[2,1-b]quinazoline-6,12-dione;Couroupitine A;Trypanthrine;NSC 349447
• CAS NO: 13220-57-0
• Molecular Formula: C₁₅H₈N₂O₂
• Molecular Weight: 248.24
• Product Categories: Indoles and derivatives
• Mol File: 13220-57-0.mol

Chemical Properties

• Melting Point: 258 °C(Solv: ethanol (64-17-5))
• Boiling Point: 469.3°C at 760 mmHg
• Flash Point: 237.7°C
• Appearance: faint yellow to dark yellow/
• Density: 1.45g/cm³
• Vapor Pressure: 5.55E-09mmHg at 25°C
• Refractive Index: 1.762
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble2mg/mL (warmed)
• PKA: -3.06±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: TRYPTANTHRIN(CAS DataBase Reference)
• NIST Chemistry Reference: TRYPTANTHRIN(13220-57-0)
• EPA Substance Registry System: TRYPTANTHRIN(13220-57-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 13220-57-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
TRYPTANTHRIN is used as an anti-inflammatory agent for its ability to inhibit cyclooxygenase COX-2 and 5-lipoxygenase, which are key enzymes involved in the inflammatory process. This makes it a potential candidate for the development of drugs to treat various inflammatory conditions.
Used in Research Applications:
TRYPTANTHRIN is used as a primary reference substance in research settings to study its anti-inflammatory properties and potential applications in drug development. Its assigned absolute purity makes it an ideal candidate for experiments and analysis.
Used in Drug Development:
TRYPTANTHRIN is used as a starting point for the development of new drugs targeting inflammation and related conditions. Its potent inhibitory effects on key enzymes involved in inflammation make it a promising candidate for further research and development.
Used in Natural Products Industry:
TRYPTANTHRIN is used in the natural products industry as a natural alkaloid with potential health benefits. Its anti-inflammatory properties can be leveraged to create natural supplements and products for managing inflammation and promoting overall health.

Biochem/physiol Actions

Tryptanthrin is a plant alkaloid with anti-inflammatory and anti cancer activities. Tryptanthrin blocks leukotriene production in neutrophils and in whole blood assays, and in an in vivo rat pleurisy model. The compound also inhibits P-glycoprotein, and sensitizes resistant cancer cell lines to killing by cytotoxic agents.

in vitro

in human hepatocyte-derived hepg2 cells, tryptanthrin inhibited the reactive oxygen species formation, mitochondrial dysfunction, and cell death triggered by tert-butyl hydroperoxide (tbhp). furthermore, tryptanthrin reversed the reduction of glutathione (gsh) induced by tbhp. specifically, nuclear translocation, transactivation of nuclear factor erythroid 2-related factor 2 (nrf2), and phosphorylation of extracellular signal-regulated kinase (erk) were evoked by the treatment of tryptanthrin. additionally, the expression of the heme oxygenase 1 and glutamate was upregulated by tryptanthrin [1].

in vivo

balb/c (h-2d) mice, intraperitoneally (i.p.) inoculated with leukemia wehi-3b jcs cells, were injected i.p with tryptanthrin at doses of 0.04 mg/kg, 0.08 mg/kg and 0.16 mg/kg body weight for 5 consecutive days. tryptanthrin inhibited the growth of wehi-3b jcs cells in balb/c mice, and at the dosages of 0.08 mg/kg and 0.16 mg/kg, significant inhibition was seen. moreover, tryptanthrin, in a dose-dependent fashion, triggered cell cycle arrest of the wehi-3b jcs cells at g0/g1 phase [2].

References

Sen, Mahato, Dutta, Tetrahedron Lett., 609 (1974)

InChI:InChI=1/C15H8N2O2/c18-13-10-6-2-4-8-12(10)17-14(13)16-11-7-3-1-5-9(11)15(17)19/h1-8H

Upstream product

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• 85291-61-8 12H-Chinolino<2,1-b>chinazolin-12-on 
• 6411-55-8 2-phenylimino-indolin-3-one 
• 91-56-5 indole-2,3-dione 
• 482-89-3 1H,1H'-2,2'-Biindolylidene-3,3'-dione 
• 119072-54-7 2,6-dimethylphenyl isonitrile 
• 60941-84-6 Sulfinamide Anhydride of Anthranilic Acid 
• 59-48-3 2-oxoindole 

Downstream Products

• 91-56-5 indole-2,3-dione 
• 118-92-3 anthranilic acid 
• 1447589-61-8 (5aS,6S)-6-hydroxy-6-(2-((S)-5-isopropyl-2-oxo-3-((R)-1-phenylethyl)imidazolidin-1-yl)-2-oxoethyl)-5a,6-dihydroindolo[2,1-b]quinazolin-12(5H)-one 
• 1447589-60-7 (S)-6-hydroxy-6-(2-((S)-5-isopropyl-2-oxo-3-((R)-1-phenylethyl)imidazolidin-1-yl)-2-oxoethyl)indolo[2,1-b]quinazolin-12(6H)-one 
• 65618-07-7 2,8-dibromoindolo[2,1-b]quinazoline-6,12-dione 

Relevant articles and documents

Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides

Based on a common structural core of 4,5,6,7-Tetrahydro[1,2,3]triazolo[1,5-A]pyridine, a number of bicyclic triazolium ionic liquids 1-3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides.

Cytotoxicity and reversal of multidrug resistance by tryptanthrin-derived indoloquinazolines

Aim: To evaluate the effects and elucidate the mechanisms of a series of indoloquinazolines as novel anticancer agents. Methods: Condensation of the substituted isatoic anhydride with the substituted isatin was performed to prepare compounds 1-4, followed by adding malononitrile to prepare compounds 5-7. Cytotoxicity was measured by MTT assays. Apoptosis induction was evaluated using DNA fragmentation, cell cycle assay, caspase 3/7 activity and Western blot. Results: Compounds 3, 4, and 5 display cytotoxicity against MCF-7, HeLa, SKOV3, and A498 cancer cells. DNA ladders appear in cells treated with compounds 3, 4, and 5. Within those, compound 4 exhibits the greatest activity in regards to sub-G 1 accumulations in the cell cycle and the activation of caspase-3/7. Furthermore, Fas and Fas ligand levels are elevated by compound 4, implying that the apoptosis is in part mediated through the signals. On the other hand, compounds 1 and 7 display chemosensitizing activity since cytotoxicity of doxorubicine and etoposide is enhanced in combination with compound 1 and 7, respectively, in MCF-7/adr (doxorubicin-resistant) and MCF-7/vp (etoposide-resistant). Conclusion: The cytotoxicity of indoloquinazolines is structure-dependent rather than cell type-dependent due to the similar degree of cytotoxicity induced by the individual compounds in all four cell lines. Further modification of the tryptanthrin skeleton is important to develop novel anticancer agents bearing either cytotoxicity against MCF-7 cells or drug resistance reversal in MCF-7/adr and MCF-7/vp.

Conversion of Isatins to Tryptanthrins, Heterocycles Endowed with a Myriad of Bioactivities

The numerous bioactivities exhibited by tryptanthrins led chemists to develop synthetic approaches towards this important scaffold. In particular, conversion of isatins into tryptanthrins has been the subject of several studies. In this context, by using iodine and potassium hydroxide at room temperature, we have discovered a simple way to convert isatin and seven of its 5-substituted derivatives (Bu, F, Cl, Br, I, OMe and OCF3) into the corresponding tryptanthrins. Furthermore, a mechanism was proposed to explain this original reactivity. Finally, we evaluated the antibacterial, antifungal, antioxidant and cytotoxic properties of the synthesized tryptanthrins. The unprecedented inhibition of human 20S constitutive proteasome was finally evaluated.

One-pot, four-component synthesis of spiroindoloquinazoline derivatives as phospholipase inhibitors

An efficient, one-pot, two-step, four-component reaction for the synthesis of spiroindoloquinazoline derivatives in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) is described. The syntheses are achieved by the condensation reaction of isatin derivatives, isatoic anhydride, malononitrile and carbonyl compounds under reflux in acetonitrile. Several of the resulting compounds showed moderate activity as phospholipase A2 inhibitors.

Electrosynthesis of tryptanthrin

Tryptanthrin is obtained in a high yield by cathodic reduction of isatin via a low-energy consumption process where an electron transfer to the oxygen in air is involved.

I2/NaH/DMF as oxidant trio for the synthesis of tryptanthrin from indigo or isatin

Tryptanthrin, a product present in several natural sources used as colorants and very relevant in the field of Medicinal Chemistry, was synthesized from indigo and isatin under mild conditions using microwave irradiation. A plausible mechanism for the synthesis of tryptanthrin using the oxidant system formed by iodine, sodium hydride and DMF, the latter acting with dual activity as solvent and as the oxygen source, is proposed.

1-Butyl-2-methylpipyridinium iodide ([BMPPY]I): novel ionic liquid for the synthesis of 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-ones under green solvent-free conditions

Abstract: In this article we reported preparation of 1-butyl-2-methylpipyridinium iodide ([BMPPY]I), as a novel ionic liquid (IL) through simple procedure. This newly prepared IL has been characterized by FT-IR, FESEM, EDX, TGA/DTG, 1H NMR, 13C NMR, and Gc-mass techniques. The FESEM images revealed nano scale for the IL with the average diameter of 150–185?nm. Its efficacy examined for the synthesis of 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-ones via domino three-component reaction of isatin derivatives, isatoic anhydride, and indoles under solvent-free conditions at 100?°C. The results affirmed that ([BMPPY]I) possessed a dual catalytic/solvent role to promote this condensation. Non-flammability, thermal stability, non-toxicity and low cost of the IL that led to obtain pharmaceutically-active heterocycles though easy work-up procedure and short reaction times, are some highlighted features of this green protocol. Graphical abstract: [Figure not available: see fulltext.].

An I2-mediated cascade reaction of 2′-bromoacetophenones with benzohydrazides/benzamides leading to quinazolino[3,2-b]cinnoline or tryptanthrin derivatives

An efficient and facile protocol for the synthesis of quinazolinone-fused tetracyclic compounds through an iodine-mediated one-pot cascade reaction of 2′-bromoacetophenones with 2-aminobenzohydrazides or 2-aminobenzamides is reported. With 2-aminobenzohyd

Analysis of stereoelectronic properties, mechanism of action and pharmacophore of synthetic indolo[2,1-b]quinazoline-6,12-dione derivatives in relation to antileishmanial activity using quantum chemical, cyclic voltammetry and 3-D-QSAR CATALYST procedures

Several indolo[2,1-b]quinazoline-6,12-dione (tryptanthrin) derivatives exhibited remarkable activity at concentrations below 100 ng/mL when tested against in vitro Leishmania donovani amastigotes. The in vitro toxicity studies indicate that the compounds are fairly well tolerated in both macrophage and neuronal lines. An analysis based on qualitative and quantitative structure-activity relationship studies between in vitro antileishmanial activity and molecular electronic structure of 27 analogues of indolo[2,1-b]quinazoline-6,12-dione is presented here by using a combination of semi-empirical AM1 quantum chemical, cyclic voltammetry and a pharmacophore generation (CATALYST) methods. A modest to good correlation is observed between activity and a few calculated molecular properties such as molecular density, octanol-water partition coefficient, molecular orbital energies, and redox potentials. Electron transfer seems to be a plausible path in the mechanism of action of the compounds. A pharmacophore generated by using the 3-D QSAR of CATALYST produced a fairly accurate predictive model of antileishmanial activity of the tryptanthrins. The validity of the pharmacophore model extends to structurally different class of compounds that could open new frontiers for study. The carbonyl group of the five- and six-membered rings in the indolo[2,1-b]quinazoline-6,12-dione skeleton and the electron transfer ability to the carbonyl atom appear to be crucial for activity.

Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O2

A metal-free catalytic approach to tryptanthrins has been achieved for the first time. The unique process is realized by an organocatalytic and indole and anthranilic acid substrate co-catalyzed photochemical oxidative condensation with visible light and O2. The truly environmentally friendly reaction conditions enable various reactants to participate in the process to deliver structurally diverse tryptanthrins.