478-43-3 Usage
Description
Rhein is a naturally occurring compound that can be found in the form of yellow needles or a yellow-brown powder. It is derived from plants and has been identified for its various biological activities, making it a valuable component in the pharmaceutical and health industries.
Uses
Used in Pharmaceutical Industry:
Rhein is used as a medical intermediate for the development of various pharmaceutical products. Its presence in this industry is attributed to its ability to inhibit growth factor beta-1 induced plasminogen activator inhibitor-1 in endothelial cells, which can have significant implications for the treatment of certain medical conditions.
Used in Health Food Industry:
Rhein is also utilized as a raw material in the health food industry. Its inclusion in this sector is due to its potential benefits for overall health and well-being, although the specific reasons for its use may vary depending on the product formulation.
Used in Antimicrobial Applications:
Rhein acts as an antibacterial agent, particularly against Staphylococcus aureus. This application is significant in the context of combating bacterial infections and promoting overall health.
Used in Laxative Formulations:
Furthermore, Rhein is employed as a laxative, helping to alleviate constipation and promote regular bowel movements.
Used in Cellular Research:
Rhein has been used to induce a necrosis-apoptosis switch in injured pancreatic acinar cells. This application is relevant in the field of cellular biology and may contribute to a better understanding of cell death mechanisms and potential therapeutic interventions.
Physical and Chemical Properties
The chemical name of Rhein is 1,8-dihydroxy anthraquinone-3-carboxylic acid, with the molecular formula C15H8O6 and the molecular weight of 284.21. It becomes yellow acicular crystal after sublimation, with the melting point 321~322 ℃ and decomposition temperature 330 ℃ and UVλmax (methanol) 229, 258, 435nm. It is soluble in alkali and pyridine, and slightly soluble in alcohol, ether, benzene, chloroform, petroleum ether, and insoluble in water. It can form red sylvine and pink sodium salt, and form a red precipitate with calcium hydroxide and barium hydroxide.
Production Method: being acquired from the hydrolysis of Rhein diacetic ester.
diethyl acetate. Uses: Current clinical treatment of rheumatic drugs often contain Rhein.
Rhein is extracted from the root of the plant Rheum palmatum L. in Polygonaceae family, which is a anthraquinones and has the functions of antibacterial, anti-cancer, cathartic, and diuretic. The contents of rhein, aloe-emodin and rheum emodin in rhubarb are listed in the following table:
Table 1. The contents of rhein, aloe-emodin and rheum emodin in rhubarb (n=2%).
Pharmacological effects
There are chemical compounds chrysophanic acid, rhein, aloe-emodin, rheum emodin, aloe emodin, and Sennoside in rhubarb.
Both the rhein and rheum emodin have the anti-tumor effect, especially a strong inhibitory effect for melanoma and they have certain inhibition on breast cancer and ehrlich’s ascites carcinoma. When rhein was applied to intratumoral administration in mice with breast cancer, there was a significant damaging in the cancer tissue. The inhibition rate of 5mg/kg rhein and rheum emodin on murine melanoma was 76% and 73%, respectively. Rheum emodin has significant competitive inhibition on tyrosinase, and this inhibition may be one of the mechanisms why rhubarb has the anti-melanoma effect. At the concentration of 10μg/ml, Rheum emodin significantly inhibited the cell division and DNA biosynthesis of human lung cancer A-549 cells. After the subcutaneous injection of crude extracts of rhubarb, an inhibition of mouse sarcoma S37 was found. The inhibition rate of Rhein on ehrlich’s ascites carcinoma and sarcoma S180 in mice was 15% and 21%, respectively. The inhibition rate of hot water extracts of Rhubarb on sarcoma S180 in mice was 48.8%.
Rhein has inhibition effect on mouse leukemia P388. Rhein, aloe-emodin and rheum emodin are extracted from rhubarb and these three anthraquinone derivatives could minimize the amount of ascites and the number of cancer cells in different extent in mice with tumors, among which the effect of rhein was most obvious and the effect of aloe-emodin was poorer, with a almost parallel relationship with prolonged survival time. The inhibition of rhein and rheum emodin on biosynthesis of DNA, RNA and protein was stronger, whereas the inhibition of aloe-emodin was weaker.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Rhein forms a red potassium salt and a pink sodium salt.
Hazard
Low toxicity by ingestion.
Fire Hazard
Flash point data for Rhein are not available; however, Rhein is probably combustible.
Biochem/physiol Actions
Constituent that is enriched in rhubarb with anti-inflammatory, anti-osteoarthritic, and anti-cancer activity. It reduces IL-1β production and secretion, caspase-3 activity, inducible nitric oxide synthase activity, and phosphorylation of c-Jun and c-Jun NH2-terminal kinase (JNK).
Safety Profile
A poison by intravenous route. Low toxicity by ingestion. When heated to decomposition it emits acrid smoke and irritating vapors.
Check Digit Verification of cas no
The CAS Registry Mumber 478-43-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,7 and 8 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 478-43:
(5*4)+(4*7)+(3*8)+(2*4)+(1*3)=83
83 % 10 = 3
So 478-43-3 is a valid CAS Registry Number.
InChI:InChI=1/C15H8O6/c16-9-3-1-2-7-11(9)14(19)12-8(13(7)18)4-6(15(20)21)5-10(12)17/h1-5,16-17H,(H,20,21)/p-1
478-43-3Relevant articles and documents
Synthesis and pharmacokinetic profile of rhein- boswellic acid conjugate
Suneela, Dhaneshwar,Dipmala, Patil
, p. 7582 - 7587 (2012)
Rhein, an active metabolite of diacerein, down-regulates the gene-expression and production of pro-matrix metalloproteinases and up-regulates the tissue inhibitors of metalloproteinase-1 production. The therapeutic effects of diacerein on osteoarthritis are, at least in part, due to the chondroprotective effect of rhein. Boswellic acid is a specific, non-redox inhibitor of leukotriene synthesis. It is claimed to possess good anti-inflammatory, anti-arthritic, analgesic, and anti-ulcer activities. It prevents the destruction of articular cartilage by decreasing degradation of glycosaminoglycans. Therefore, rhein and boswellic acid were linked chemically through a bioreversible ester linkage to synthesize their mutual prodrug by reported procedure. In vitro release profile of this prodrug was extensively studied in aqueous buffers of varied pH, upper GIT homogenates and 80% human plasma. In vivo release studies were undertaken in blood, urine and feces of rats. The prodrug was stable in HCl buffer (pH 1.2) and stomach homogenates of rats. However; in phosphate buffer (pH 7.4) and in intestinal homogenates the prodrug exhibited 91% and 96% release of rhein and 27.5% and 38% release of boswellic acid respectively over a period of 6 h following first order kinetics. In 80% human plasma (in vitro) and rat blood (in vivo) also 96.35% and 91% release of rhein and 78% and 86.41% release of boswellic acid respectively was observed. The 24 h pooled samples of rat urine revealed presence of 6.2% intact prodrug, 7.1% of rhein and 8.9% of boswellic acid indicating their renal excretion. Samples of rat feces pooled over a period of 24 h showed absence of rhein and presence of 3.1% of intact boswellic acid and 4.6% of boswellic acid emphasizing their intestinal excretion. The in vivo release kinetics of prodrug in rat clearly indicated activation of prodrug to be occurring in blood, being catalyzed by the weak alkaline pH of blood (7.4) in combination with esterases present therein.
Oesterle,Riat
, p. 527 (1909)
Synthesis of rhein and diacerein: a chemoenzymatic approach using anthrol reductase of Talaromyces islandicus
Rajput, Anshul,Mondal, Amit,Pandey, Satyendra Kumar,Husain, Syed Masood
supporting information, p. 358 - 361 (2022/01/20)
Herein, we report two methods for the synthesis of the osteoarthritis drug rhein and its prodrug diacerein using a chemoenzymatic approach. The strategy relies on the use of an NADPH-dependent anthrol reductase of Talaromyces islandicus (ARti-2), which mediates the regioselective and reductive deoxygenation of anthraquinones. The work further implies similar biosynthesis of rhein in fungi.
Synthetic process of rhein
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Paragraph 0018, (2018/03/26)
The invention relates to a total synthetic process of rhein. The synthetic process comprises the steps of: performing diene synthesis on juglone and 3-M-1-(methoxy)-1,3-butadiene to obtain a mixture,performing refining, and conducting hydrolysis to obtain rhein.