478-43-3Relevant academic research and scientific papers
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.
A biocatalytic approach towards the preparation of natural deoxyanthraquinones and their impact on cellular viability
Das, Kiran,De, Arijit,Husain, Syed Masood,Maity, Biswanath,Mondal, Amit,Rajput, Anshul
, p. 3087 - 3090 (2022/02/21)
Herein, a two-step chemoenzymatic process for the synthesis of medicinally important 3-deoxygenated anthra-9,10-quinones is developed. It involves a regio- and stereoselective reduction of hydroanthraquinones to (R)-configured dihydroanthracenones using an anthrol reductase of T. islandicus, followed by oxidation and dehydration to obtain deoxyanthraquinones in 65-80% yield. Comparison of the cell viability of normal human kidney HEK293 cells between anthraquinones and their deoxy derivatives revealed less toxicity for the latter.
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.
Bis(methoxypropyl) ether-promoted oxidation of aromatic alcohols into aromatic carboxylic acids and aromatic ketones with O2 under metal- and base-free conditions
Liu, Kai-Jian,Jiang, Si,Lu, Ling-Hui,Tang, Ling-Li,Tang, Shan-Shan,Tang, Hai-Shan,Tang, Zilong,He, Wei-Min,Xu, Xinhua
supporting information, p. 3038 - 3043 (2018/07/13)
We describe an eco-friendly, practical and operationally simple procedure for the bis(methoxypropyl) ether-promoted oxidation of aromatic alcohols into aromatic carboxylic acids and aromatic ketones with atmospheric dioxygen as the sole oxidant. This chemical process is clean with high conversion and good selectivity, and an external initiator, catalyst, additive and base are not required. The virtue of this reaction is highlighted by its easily available and economical raw materials and excellent functional group tolerance (acid-, base- and oxidant-labile groups).
Industrial production method suitable for diacerein
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, (2018/07/30)
The invention discloses an industrial production method suitable for diacerein. A compound as shown in a formula I is obtained after carrying out secondary oxidation on raw materials. The industrial production disclosed by the invention overcomes the disadvantages of excessive heavy metal, serious pollution, and inflammability and explosibility of a finished product prepared through a synthesis route reported in existing literatures; a reagent used by the industrial production method is low in cost, environment pollution is small, the operation is easy, and the industrial production method issuitable for industrial production; a product is good in quality, total impurities are less, the content of single impurity is controlled to be 0.1 percent or less, the finished product is controlledto be in a single and stable crystal form, and the requirements of medicinal-class bulk drugs can be met.
Total synthesis process of rhein
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, (2017/08/29)
The invention relates to a total synthesis process of rhein. The process includes: adopting methoxy phthalic anhydride and a Grignard reaction liquid as the raw materials, and carrying out condensation, dehydration cyclization, methoxylation, oxidation and demethylation reaction so as to obtain rhein.
Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes
Petralito, Stefania,Zanardi, Iacopo,Spera, Romina,Memoli, Adriana,Travagli, Valter
, p. 355 - 360 (2014/04/03)
Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HPβCD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HPβCD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution.
Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors
Shi, Da-Hua,Huang, Wei,Li, Chao,Liu, Yu-Wei,Wang, Shi-Fan
, p. 289 - 296 (2014/03/21)
A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout.
Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors
Shi, Da-Hua,Huang, Wei,Li, Chao,Wang, Ling-Ting,Wang, Shi-Fan
, p. 1064 - 1073 (2013/03/14)
A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC50 = 0.09 μM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.
