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
• Article Data: 85

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

Description

The matured fruit of Couroupita guianensis yields two highly unsaturated alkaloids. Couroupitine A is obtained in the form of yellow needles when crystallized from MeOH-CHCI3. It gives an ultraivolet spectrum with absorption maxima at 225 and 251 nm and an inflexion at 315 nm in EtOH.

Uses

Tryptanthrin is natural alkaloid, and a potent inhibitor of cyclooxygenase COX-2 and 5-lipoxygenase acting as an anti-inflammatory agent.

General Description

This substance is a primary reference substance with assigned absolute purity (considering chromatographic purity, water, residual solvents, inorganic impurities). The exact value can be found on the certificate. Produced by PhytoLab GmbH & Co. KG

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

• 6245-93-8 3-hydroxy-1H-indole-2-carboxylic acid 
• 612-27-1 2-nitroso-benzoic acid 
• 91-56-5 indole-2,3-dione 
• 119072-54-7 2,6-dimethylphenyl isonitrile 
• 60941-84-6 Sulfinamide Anhydride of Anthranilic Acid 
• 118-92-3 anthranilic acid 
• 120-72-9 indole 
• 68-12-2 N,N-dimethyl-formamide 
• 34897-85-3 o-azidobenzoyl chloride 
• 123767-94-2 anthraniloyl chloride ; hydrochloride 
• 31162-13-7 2-azidobenzoic acid 
• 83-34-1 3-Methylindole 
• 2142-69-0 2-bromophenyl methyl ketone 
• 28144-70-9 anthranilic acid amide 

Downstream Products

• 113001-48-2 1-(2-acetamidobenzyl)-3-acetoxyindole 
• 113001-47-1 6-acetoxy-5-acetyl-5,5a,6,12-tetrahydroindolo<2,1-b>-quinazoline 
• 77603-42-0 8-nitroindolo[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.

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.

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.

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

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.

CoCl2-promoted TEMPO oxidative homocoupling of indoles: Access to tryptanthrin derivatives

A novel TEMPO/CoCl2-promoted aerobic oxidation of indoles was developed. The reaction provided one-step access to tryptanthrin derivatives in moderate to good yields and excellent regioselectivity via a cascade process. The reactions could be carried out under mild reaction conditions with varying functional group tolerance, especially halogen functional groups. Mechanistic studies disclosed that the oxygen atom in the desired product originated from molecular dioxygen.

Cobalt(III)-porphyrin complex (CoTCPP) as an efficient and recyclable homogeneous catalyst for the synthesis of tryptanthrin in aqueous media

The water soluble cobalt(III) porphyrin complex (CoTCPP) was employed as an efficient catalyst for the synthesis of the biologically active natural product tryptanthrin. The reaction proceeded under mild conditions in aqueous media at room temperature from various isatoic anhydride and isatin derivatives. The advantages of these reactions were excellent yields, short reaction times and a recoverable catalyst.

A simple synthesis of tryptanthrin

A simple synthetic procedure for tryptanthrin was established from oxindole via indolo[2,1-b]quinzolin-12(6H)-one as a key intermediate.

β-Cyclodextrin catalysed synthesis of tryptanthrin in water

An efficient and green method has been developed for the synthesis of tryptanthrin employing β-cyclodextrin as a catalyst in aqueous media at room temperature from isatoic anhydride and isatin. The reactions were performed under mild conditions to afford biologically active natural product tryptanthrin in excellent yields.

Domino Oxidative Cyclization of 2-Aminoacetophenones for the One-Pot Synthesis of Tryptanthrin Derivatives

A new CuI/DMSO-mediated oxidative domino process has been developed for the synthesis of tryptanthrin derivatives. This is the first example of the synthesis of tryptanthrin derivatives directly from 2-aminoaryl methyl ketones and isatoic anhydrides through copper-promoted oxidative functionalization. A new DMSO/CuI-catalysed oxidative domino process has been developed for the one-pot synthesis of tryptanthrin derivatives.

One-pot synthesis of simple alkaloids: 2,3-Polymethylene-4(3H)- quinazolinones, luotonin A, tryptanthrin, and rutaecarpine

One-pot synthesis of various 2,3-polymethylene-4(3H)-quinazolinones from anthranilic acid, corresponding lactam and SOCl2 is described, which can be applicable to the synthesis of simple 4(3H)-quinazolinone-derived alkaloids, such as luotonin A, tryptanthrin, and rutaecarpine.

8-Methyltryptanthrin-induced differentiation of P19CL6 embryonal carcinoma cells into spontaneously beating cardiomyocyte-like cells

Enhancement of cardiac differentiation is critical to stem cell transplantation therapy for severe ischemic heart disease. The aim of this study was to investigate whether several derivatives of tryptanthrin (1), extracted from the medicinal plant Polygonum tinctorium, induce the differentiation of P19CL6 mouse embryonal carcinoma cells into beating cardiomyocyte-like cells. P19CL6 cells were cultured in α-MEM supplemented with 10% FBS including a test compound or vehicle. Drug-induced differentiation was assessed by measuring the number of beating and nonbeating aggregates and the area of beating aggregates, and the expression of genes involved in cardiac differentiation was evaluated by real-time PCR. A 1 μM concentration of 8-methyltryptanthrin (2) induced the differentiation of P19CL6 cells into cardiomyocyte-like cells to a significantly greater degree than 1% dimethyl sulfoxide (DMSO), a conventional differentiation inducer of P19CL6 cells. Furthermore, 2 strongly increased both the number and the area of spontaneously beating aggregates in comparison with DMSO. Two distinct genes of the calcium channel family, Cav1.2 and Cav3.1, underlying cardiac automaticity were significantly expressed in the presence of 2. Gap junction genes GJA1 and GJA5 contributing to the synchronized contraction of the myocardium were also induced significantly by 2. These results suggest that 2 successfully differentiated P19CL6 cells into spontaneously beating cardiomyocyte-like cells by activating the gene expression of pacemaker channels and gap junctions.

Divergent Synthesis of Methylisatoid and Tryptanthrin Derivatives by Ph3P-I2-Mediated Reaction of Isatins with and without Alcohols

A novel phosphonium-mediated reaction of isatins is described. In the presence of alcohol, the reaction proceeds to furnish C-12 modified tryptanthrin derivatives. Without alcohol, self-dimerization of isatins gives rise to tryptanthrin and its analogs. T

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

Phaitanthrin E was biomimetically synthesized from methyl indole-3-carboxylate and methyl anthranilate or anthranilic acid using the ester group as an activating group. The reaction proceeds through NCS-mediated dearomatization/TFA-catalyzed protonation of indolenine/C(2) amination/Et3N-promoted aromatization and cyclization in one-pot procedure. This method is capable of converting simple biomass materials to phaitanthrin E. The synthesis not only allows assessment of antiproliferative activity, but also affords experimental support for the hypothetical biosynthetic pathway of phaitanthrin E. The resulting phaitanthrin E derivatives were evaluated for in vitro antiproliferative activity against human colorectal cancer cells (DLD-1). The biogenetic intermediate of phaitanthrin E showed higher antiproliferative activity than the natural product, phaitanthrin E. Furthermore, a concise synthesis of tryptanthrin is also accomplished from indole-3-carbaldehyde and methyl anthranilate using the aldehyde group as an activating group.

Synthesis and in vitro evaluation of antitumor activity of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-d]pyrimidine] and spiro[indolo[2,1-b]quinazoline-pyrido[2,3-d]pyrimidine] derivatives by using 2D and 3D cell culture models

Abstract: Cancer as one of the biggest human health problems remains unsolved. The identification of novel platforms with the highest efficacy and low toxicity is a big challenge among interested researchers. In this regard, we are interested to synthesis and evaluate antitumor activity of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-d]pyrimidine] and spiro[indolo[2,1-b]quinazoline-pyrido[2,3-d]pyrimidine] derivatives. The spiro heterocycles were synthesized via four-component reaction of isatoic anhydride, isatins, malononitrile, and some CH-acids including barbituric acid/thiobarbituric acid and 4(6)-aminouracil in CH2Cl2 under reflux condition. The significant features of this process are short reaction time, easy purification without chromatographic process, and high yields which make it attractive. Next, we employed 2D and 3D cell culture models to evaluate biological activity of our compounds. Our results showed that among our seven products (4a–g), the compounds 4a and 4e are the best with 50% growth inhibitory concentration (IC50) value lower than etoposide. Our results support this idea that the compounds 4a and 4e may be potential for drug designing in cancer therapy. However, more experiments will be required to find possible side effects of related compounds in vivo. Graphic abstract: [Figure not available: see fulltext.]

Novel tryptanthrin hybrids bearing aminothiazoles as potential EGFR inhibitors: Design, synthesis, biological screening, molecular docking studies, and ADME/T predictions

A variety of novel tryptanthrin aminothiazole analogues 3a-h and 5a-h possessing a biologically active thiazole moiety were synthesized by the reaction of tryptanthrin thiosemicarbazones with different α-bromo-4-substituted-acetophenones compounds. The structures of all the synthesized compounds were characterized by mass, 1H NMR, 13C NMR, and elemental analysis. All the novel synthesized compounds were investigated for their in vitro anticancer activity against three human cancer cell lines (MCF-7, A549, and HeLa) by taking cisplatin as a reference drug. The compounds 3b and 3c displayed excellent anticancer activities against the growth of three human cancer cell lines. EGFR targeting molecular docking investigation revealed that tryptanthrin aminothiazole analogues have better binding energies compared with EGFR inhibitors (Gefitinib, Erlotinib, and Lapatinib). The molecular docking findings back up the experimental anticancer activity results very well. The compounds were also tested for their antibacterial and antioxidant activities. In silico ADMT predictions have been performed that these tryptanthrin aminothiazole analogues have a good pharmacokinetic profile.