Indirubin Chemical Properties

Melting point:

350°C(lit.)

Boiling point:

496.6±45.0 °C(Predicted)

Density 

1.417±0.06 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMSO (Slightly), Methanol (Very Slightly, Heated)

pka

9.13±0.20(Predicted)

form 

Purple powder.

color 

Very Dark Red

λmax

540nm(DMSO)(lit.)

InChI

InChI=1S/C16H10N2O2/c19-15-10-6-2-4-8-12(10)17-14(15)13-9-5-1-3-7-11(9)18-16(13)20/h1-8,17H,(H,18,20)

InChIKey

CRDNMYFJWFXOCH-UHFFFAOYSA-N

SMILES

N1C2=C(C=CC=C2)C(=C2C(=O)C3=C(N2)C=CC=C3)C1=O

CAS DataBase Reference

479-41-4(CAS DataBase Reference)

Safety Information

RTECS 

DU2995000

HS Code 

29339900

Indirubin Usage And Synthesis

Description

Indirubin is the active ingredient of Danggui Longhui Wan, a traditional Chinese medicine containing plants such as Indigofera tinctoria L. and Isatis tinctoria L, which are used in traditional Chinese medicine to treat chronic diseases. Indirubin and its analogues are reported as potent inhibitors of cyclin-dependent kinases (CDKs). This could attribute to the positive effect of indirubin on counteracting proliferative diseases, such as chronic myelocytic leukemia (CML), a slowly progressive disease characterized by the overproduction of granulocytes.

References

[1] Tina Bla?evi?, Elke H. Heiss, Atanas G. Atanasov, Johannes M. Breuss, Verena M. Dirsch and Pavel Uhrin, Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases, Evidence-Based Complementary and Alternative Medicine, 2015, vol. 2015, Article ID 654098
[2] Ralph Hoessel, Sophie Leclerc, Jane A. Endicott, Martin E. M. Nobel, Alison Lawrie, Paul Tunnah, Maryse Leost, Eve Damiens, Dominique Marie, Doris Marko, Ellen Niederberger, Weici Tang, Gerhard Eisenbrand and Laurent Meijer, Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases, Nature Cell Biology, 1999, vol. 1, 60-67

Description

A further alkaloid isolated from the matured fruit of Couroupita guianensis, this base forms red crystals from EtOH and melts above 340°C. It forms the Nacetyl derivative, m.p. 186°C. The full structure has not yet been established.

Physical properties

Appearance: dark red acicular crystal with sublimate, odorless, and tasteless. Solubility: slightly soluble in dimethyl sulfoxide (DMSO) or tetrahydrofuran, very slightly soluble in chloroform or acetone, and insoluble in ethanol, ethyl ether, or water. Melting point: 348–353 °C. The stability of indirubin is poor that it needs to be stored away from light and thermal environment.

History

The report in 1951 showed that indirubin can inhibit eosinophils in the blood of guinea pigs. But this report did not attract attention. Indirubin is the effective component of the traditional Chinese medicine Angelica aloe pill. Since 1966, the scientists in the Institute of Hematonosis, Chinese Academy of Medical Sciences Research, started the research of therapying chronic myelocytic leukemia with the TCM rules using Angelica aloe pills, which had certain effect. Angelica aloe pill consisted of 11 herbs, such as Angelica, Aloe, Rhizoma Coptidis, and natural indigo. It was identified that natural indigo was the effective component of Angelica aloe pill. However, the active ingredient of natural indigo was indirubin.
Indirubin is a novel antileukemia drug, which was found by the medical scientists in China in the middle of the 1970s. It has the effects of antibacterial, antiinflammatory, antitumor, and enhancing immune functions. The compound has been applied to the clinical treatment of chronic myeloid leukemia. Indirubin has the characteristics of reliable clinical curative effect, small side effects, and no obvious inhibitory effect on the bone marrow.

Uses

Indigopurpurin is a purple 3,2-bisindole derivative and was shown to exhibit inhibitory allergic contact dermatitis via regulating T helper (Th)-mediated immune system in DNCB-induced model. A possible glycogen synthase kinase-3 (GSK-3) inhibitor the active component of a traditional Congolese antiepilepsy treatment.

Uses

An inhibitor of GSK-3β and cyclin-dependent kinases.

Indications

Indirubin is contained in the fourth volume of the book, “National standards for chemical drugs.”
Indirubin tablets are used for the therapy of chronic myelocytic leukemia in clinical.

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

Pharmacology

The effect of indirubin has anti-inflammatory, antibacterial, detoxification, enhancing immune function anticancer. Indirubin has moderate inhibitory effect for animal-transplanted tumor. 200? mg/kg indirubin subcutaneous or intraperitoneal injection, once daily for 6 consecutive days, had the inhibition effect to rat W256 tumor cancer sarcoma; the inhibition rates were 47–52% and 50–58%, respectively. The chemotherapy index of intraperitoneal injection was 2.23. However, the inhibition rate of 500?mg/kg indirubin by gavage was only 23–33%. Indirubin by perfusion can prolong the survival time of W526 rat. The inhibition rate of Lewis mice’s lung cancer was 43% for 500?mg/kg indirubin orally, once a day for 9–10?days. Indirubin has some inhibition effects on mice breast cancer, but no obvious effect for L1212, P388, and L1210 of lymphocytic leukemia in mice.
The effect of indirubin on chronic myelogenous leukemia is very obvious, which is similar to first clinical choice of Maryland. Indirubin has the advantages of fast curative effect, no obvious inhibition effect of the bone, small bone marrow toxicity, and low side effects. Indirubin may have the effect of improving adrenocorticotropic hormone. In pathological conditions, such as inflammatory diarrhea, protein metabolism disorder, kidney disease, leukemia, and other tumors, urinary excretion of indirubin increased. Indirubin can inhibit synthesis of DNA and destroy the leukemia cells. It was found by electron microscopy that juvenile cells reduced, even disappear completely, with indirubin administration. Indirubin can significantly reduce the size of spleen, increase the concentration of hemoglobin to normal level, and reduce the swelling liver. In addition, indirubin can also enhance the phagocytic ability of animal mononuclear macrophages, which play a role in body immune reaction. So the anticancer effect of this product may be related to improving the body’s immunity.

Clinical Use

Indirubin is mainly used for chronic myeloid leukemia; its total effective rate was 87.3%. The effect of indirubin to decrease white blood cells is similar to Maryland. The effect of indirubin to reduce liver is better than that of Maryland. But the remission role of the blood and bone marrow is worse than Maryland, and no cross resistance with Maryland. Indirubin could be used for abnormal bone marrow hyperplasia and eosinophilia.

in vitro

indirubin exerted its inhibitory effects not only on interferon-γ production by human myelomonocytic hbl-38 cells but also on interferon-γ and interleukin-σ production by murine splenocytes with no influence on the proliferation of either cells [1].

in vivo

because of indirubin’s inhibitory activity on interferon-γ production, the authors further investigated the effects of indirubin on 2,4,6-trinitro-l-chlorobenzene-induced delayed-type hypersensitivity. when injected intraperitoneally, indirubin significantly inhibited the ear swelling of tncb-elicited mice. moreover,the amount of interferon-γ in the culture supernatants of elicited mouse lymphocytes was inhibited by indirubin treatment [1].

References

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

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