13739-02-1Relevant articles and documents
Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer's disease
Li, Su-Yi,Jiang, Neng,Xie, Sai-Sai,Wang, Kelvin D. G.,Wang, Xiao-Bing,Kong, Ling-Yi
, p. 801 - 814 (2014)
A series of tacrine-rhein hybrid compounds have been designed and synthesized as novel multifunctional potent ChE inhibitors. Most of the compounds inhibited ChEs in the nanomolar range in vitro effectively. Compound 10b was one of the most potent inhibitors and was 5-fold more active than tacrine toward AChE, and it also showed a moderate BuChE inhibition with an IC50 value of 200 nM. Kinetic and molecular modeling studies of 10b also indicated that it was a mixed-type inhibitor binding simultaneously to the active and peripheral sites of AChE. In inhibition of the AChE-induced Aβ aggregation assay, compound 10b (70.2% at 100 μM) showed the greatest inhibitory activity. In addition, 10b showed metal-chelating property and low hepatotoxicity. These results suggested that 10b might be an excellent multifunctional agent for AD treatment.
Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption
Xu, Xing,Qi, Xueyu,Yan, Yufei,Qi, Jin,Qian, Niandong,Guo, Lei,Li, Changwei,Wang, Fei,Huang, Ping,Zhou, Hanbing,Jiang, Min,Yang, Chunhao,Deng, Lianfu
, p. 769 - 776 (2016)
Approaches of targeting excessive activation and differentiation of osteoclasts were considered as an effective treatment option for osteoporosis or osteopenia. In the present work, a series of rhein derivatives were synthesized and employed for their cytotoxicity screening against bone marrow-derived macrophages cells (BMMs) and their inhibition effects on osteoclasts activation and differentiation in?vitro using an MTT assay and a TRAP activity assay respectively. Two rhein derivatives d6 and d11 inhibited BMMs activation and differentiation with 98% and 85% inhibitory activity respectively, without showing any cytotoxicity on BMMs. Subsequently, the most potent compound d6 was further validated for its inhibitory effects on the formation of TRAP-positive multinucleated cells and bone resorption as evaluated by TRAP staining and bone resorption assay. The regulation by d6 of osteoclast marker genes assay revealed that treatment of BMMs with M-CSF and RANKL resulted in the stimulation of mRNA expressions of NFATc1, c-fos, TRAP, MMP-9 and cathepsin K which were highly related with osteoclast activation and differentiation, while d6 decreased mRNA expressions of these genes. It was indicated that d6 might regulate osteoclasts activity through RANKL/RANK/NFATc1 pathway. Thus our current work is expected to provide a highly promising approach for the development of a new type of anti-osteoporosis agent.
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.
Diacerein synthesis method based on anthraquinone medicines
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Paragraph 0023; 0024; 0029, (2020/07/27)
The invention belongs to a medicine preparation technology, and particularly relates to a diacerein synthesis method based on anthraquinone medicines. The method comprises that aloe-emodin undergoes an oxidation reaction to obtain aldehyde aloe-emdion, aldehyde aloe-emdion undergoes an acylation reaction to obtain diacetyl aldehyde aloe-emdion, diacetyl aldehyde aloe-emdion undergoes an oxidationreaction to obtain a diacerein crude product, and the diacerein crude product is recrystallized to form the diacerein. The invention provides a process for preparing diacerein with low genotoxic impurity residue, which avoids using a resin adsorption or column chromatography purification means, also avoids using a large amount of solvent for continuous extraction and washing, can achieve the purpose by direct recrystallization, and is easy for industrial large-scale production. The content of aloe-emodin and the content of aldehyde aloe-emdion in the prepared diacerein final product are both lower than 15 ppm, and the total genotoxic impurity content is lower than 20 ppm.
Industrial production method suitable for diacerein
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Paragraph 0038-0040; 0049-0051; 0060-0062; 0071; 0072; 0073, (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.
A kind of rhubarb acid thioamide compound, its preparation and use (by machine translation)
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Paragraph 0041, (2017/11/16)
The invention relates to a has the following general structure of the rhubarb acid thioamide compound, at the same time the invention provides a preparation method thereof and use, its preparation method is simple, the rhubarb acid thioamide compounds can be improved at the same time H in vivo2 S level, and inhibits osteoclast formation. (by machine translation)
Rhein type compound and purpose thereof
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Paragraph 0125; 0126; 0127; 0128, (2017/06/19)
The invention relates to a rhein type compound and a purpose thereof. Concretely, the invention relates to the rhein type compound with the general structure formula. The rhein type compound provided by the invention can be used for preparing medicine for preventing and/or treating diseases caused by osteoclast activity abnormality. The structure formula is shown as the accompanying drawing.
Synthesis and antitumor activities of novel diacerein α-aminophosphonates conjugates
Qin, Jian-Mei,Li, Jian-Fei,Ye, Man-Yi,Huang, Ri-Zheng,Xu, Qing,Pan, Ying-Ming,Wang, Heng-Shan,Yao, Gui-Yang
, p. 1584 - 1595 (2015/02/02)
Several diacerein α-aminophosphonates conjugates 4a-k have been synthesized, the structures of compounds have been characterized by IR, 1H NMR, 13C NMR, 31P NMR, ESI-MS spectra and elementary analysis. In vitro cytotoxicity against HepG-2, CNE, Spca-2 and Hct-116 cells are evaluated and employing standard MTT assay in comparing with commercial anticancer drug 5-fluorouracil (5-FU). Some compounds exhibit moderate to high levels of antitumor activity. Especially, compound 4i exhibit the strongest cytotoxicity against Hct-116 cells with IC50 9.83 μM. All the synthesized compounds exhibit low cytotoxicity against HUVEC cells. The mechanism of compound 4i has been preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicate that the compound 4i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis show that compound 4i mainly arrested Hct-116 cells in G1 stage. The effects of 4i on the activation of caspases expression indicate that 4i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 4i to DNA have been investigated by methods (UV-Vis, fluorescence, CD spectroscopy) in comparison with that of diacerein. Results indicate that 4i show moderate ability to interact ct-DNA.
Synthesis and hypoglycemic activity evaluation of rhein amide derivatives
Zhu, Xiaokang,Ye, Xiaoli,Song, Liu,Luo, Yonghuang,Tang, Qing,Jin, Yanan,Li, Xuegang
, p. 2228 - 2234 (2013/07/26)
In order to investigate the relationship of the structure and hypoglycemic activity, rhein amide derivatives 2a-2e were synthesized and their hypoglycemic activities were evaluated by glucose consumption in HepG2. Their structures were characterized by 1H-, 13C NMR, IR, mass and elemental analysis. All the compounds exhibited strong hypoglycemic activity in improving glucose consumption in HepG2 cell assays in vitro, which was influenced by the diversity of rhein amide derivatives. The compounds 2a-c, 2f, and 2g bearing heterocyclic ring were proved to be more potentially useful in glucose consumption than dimethyldiguanide. Among all the compounds, compound 2f exhibited the strongest activity on glucose consumption, while compound 2d showed the weakest activity.
Bone-targeting glycol and NSAIDS ester prodrugs of rhein: Synthesis, hydroxyapatite affinity, stability, anti-inflammatory, ulcerogenicity index and pharmacokinetics studies
Cai, Jin,Duan, Yanbing,Yu, Jia,Chen, Junqing,Chao, Meng,Ji, Min
, p. 409 - 419,11 (2020/07/30)
Although rhein and NSAIDs are potent anti-inflammatory drugs, their use has been limited by the high incidence of gastrointestinal erosions and the necessity to deliver the drug to specific sites of target organ. Using the prodrug approach, a series of rhein-NSAIDs prodrugs containing anthraquinone bone-targeting moiety were synthesized by linking rhein with NSAIDs through glycol ester. The target compounds demonstrated significant capability of binding to HAP and were hydrolytically activated in physiological conditions. Hybrid rhein-NSAIDs prodrugs exhibited significant anti-inflammatory activity, moreover, the tested compounds were also found to possess less degree of ulcerogenic potential. Our pharmacokinetic studies of 7e demonstrated this prodrug is a potential candidate for a slower and sustained release form of rhein.
