35233-17-1Relevant articles and documents
Design, synthesis, and biological evaluation of novel 6h-benzo[c]chromen-6-one derivatives as potential phosphodiesterase ii inhibitors
Tang, Long,Jiang, Jianchun,Song, Guoqiang,Wang, Yajing,Zhuang, Ziheng,Tan, Ying,Xia, Yan,Huang, Xianfeng,Feng, Xiaoqing
, (2021/05/29)
Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.
Urolithin and reduced urolithin derivatives as potent inhibitors of tyrosinase and melanogenesis: Importance of the 4-substituted resorcinol moiety
Lee, Sanggwon,Choi, Heejeong,Park, Yujin,Jung, Hee Jin,Ullah, Sultan,Choi, Inkyu,Kang, Dongwan,Park, Chaeun,Ryu, Il Young,Jeong, Yeongmu,Hwang, Yeji,Hong, Sojeong,Chun, Pusoon,Moon, Hyung Ryong
, (2021/05/29)
We previously reported (E)-β-phenyl-α,β-unsaturated carbonyl scaffold ((E)-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4-substituted resorcinol moiety as the β-phenyl group of the scaffold resulted in the greatest tyrosi-nase inhibitory activity. To examine whether the 4-substituted resorcinol moiety could impart tyro-sinase inhibitory activity in the absence of the α,β-unsaturated carbonyl moiety of the (E)-PUSC scaffold, 10 urolithin derivatives were synthesized. To obtain more candidate samples, the lactone ring in synthesized urolithins was reduced to produce nine reduced urolithins. Compounds 1c (IC50 = 18.09 ± 0.25 μM), 1h (IC50 = 4.14 ± 0.10 μM), and 2a (IC50 = 15.69 ± 0.40 μM) had greater mushroom tyrosinase-inhibitory activities than kojic acid (KA) (IC50 = 48.62 ± 3.38 μM). The SAR results suggest that the 4-substituted resorcinol motif makes an important contribution to tyrosinase inhibition. To investigate whether these compounds bind to human tyrosinase, a human tyrosinase homology model was developed. Docking simulations with mushroom and human tyrosinases showed that 1c, 1h, and 2a bind to the active site of both tyrosinases with higher binding affinities than KA. Pharmacophore analyses showed that two hydroxyl groups of the 4-substituted resorcinol entity act as hydrogen bond donors in both mushroom and human tyrosinases. Kinetic analyses indicated that these compounds were all competitive inhibitors. Compound 2a inhibited cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells more strongly than KA. These results suggest that 2a is a promising candidate for the treatment of skin pigment disorders, and show the 4-substituted resorcinol entity importantly contributes to tyrosinase inhi-bition.
Urolithin compound, preparation method, pharmaceutical composition and application
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Paragraph 0112-0121, (2021/09/04)
The invention belongs to the field of medicinal chemistry, and particularly relates to a urolithin compound, a preparation method, a pharmaceutical composition and application. The urolithin compound is a compound as shown in a general formula I or an optical isomer, an enantiomer, a diastereomer, a raceme or a raceme mixture of the compound, or a pharmaceutically acceptable salt of the compound. The urolithin compound provided by the invention has good PDE2 inhibitory activity, the enzymatic level IC50 reaches 3.67 [mu] M, and the urolithin compound can be used for treating central nervous system diseases and brain neurodegenerative process diseases, and can be used as an active component to prepare drugs for inhibiting PDE2 activity.
Urolithin A and B Derivatives as ON-OFF Selective Fluorescent Sensors for Iron(III)
Fallah, Amirhossein,Noshadi, Bahareh,Gazi, Mustafa,Gülcan, Hayrettin Ozan
, p. 113 - 120 (2020/01/06)
The detection and sensing of environmentally crucial metal ions has always been of great significance in various fields such as biological and environmental cycles. Our previous studies have indicated a new coumarin based lactone, Urolithin B (i.e., 3-Hydroxy[c]chromen-6-one) as a potent fluorescent probe for the selective detection of Iron (III). In order to question the extension of this application to other urolithins, we have synthesized the major urolithins that humans are exposed to through regular diet. Following the structure identifying studies, the compounds were tested in fluorescence titration to investigate their interaction with various metals. The results have indicated that each title compound is selective to interact with Iron (III) in ON-OFF mode, independent from the presence of another metal. Similar to the previous findings, the Job’s plots displaying the ratio of complex formation 3:2 UROs:Fe3+ have indicated the significance of the lactone group solely.
Synthesis, Characterization, Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs
Noshadi, Bahareh,Ercetin, Tugba,Luise, Chiara,Yuksel, Mine Yarim,Sippl, Wolfgang,Sahin, Mustafa Fethi,Gazi, Mustafa,Gulcan, Hayrettin Ozan
, (2020/07/24)
Urolithins (that is, hydroxy substituted benzo[c]chromen-6-one derivatives) are formed within the gastrointestinal tract following to the exposure to various ellagitannin rich diet, particularly involving pomegranate, nuts, and berries. Regarding the bioavailability deficiency of ellagitannins, the biological activities obtained through the extracts of these dietaries are attributed to the urolithin compounds, since they are bioavailable. Particularly, there are studies indicating the importance of ellagitannin-rich food for protective and alternative treatment of Alzheimer's Disease (AD). From this perspective, within this study, the major urolithins (that is, urolithins A and B), their methyl ether metabolites, as well as some synthetic urolithin analogs have been synthesized and screened for their biological activities in various enzyme inhibition (acetylcholinesterase, butyrylcholinesterase, monoamine oxidase B, cyclooxygenase 1, and cyclooxygenase 2) and antioxidant (DPPH radical scavenging) assay systems. The results pointed out the potential of urolithins to act as inhibitors on these receptors. Docking studies were also performed to investigate the possible interactions.
Urolithins as immune response enhancers
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Page/Page column 30-31, (2020/11/23)
Disclosed are compounds for use in raising an immune response to an antigen and/or enhancing, modulating or augmenting an immune response to an antigen. Particularly the use of urolithins. The invention also relates to immune enhancers comprising urolithins, methods of using such immune enhancers and processes for the preparation of such immune enhancers. The invention also relates to the use of urolithins in methods for modulating stem cell function, for example, enhancing stem cell numbers, promoting stem cell regeneration and promoting stem cell differentiation.
Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
, p. 955 - 962 (2019/02/09)
Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
METHODS FOR IMPROVING MITOPHAGY IN SUBJECTS
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Page/Page column 52, (2018/09/28)
The invention provides a compound of formula (I) wherein: A, B, C, D, W, X, Y and Z are each independently selected from H and OH; or a salt thereof; for use in the treatment and/or prophylaxis of a condition, disease or disorderin a subject, wherein the compound or salt is orally administered to a subject in adaily amount of from 1.7 to 2.7 mmol per day, over a period of at least 21 days. Also are provided are the compound of formula (l) for use in increasing mitophagy and/or autophagy, maintaining and/or improving muscle function and administration as a dietary, nutritional and/or health supplement.
METHODS FOR IMPROVING MITOPHAGY IN SUBJECTS
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Page/Page column 54, (2018/09/28)
The invention provides a compound of formula (I) wherein: A, B, C, D, W, X, Y and Z are each independently selected from H and OH; or a salt thereof; for use in the treatment and/or prophylaxis of a condition, disease or disorderin a subject, wherein the compound or salt is orally administered to a subject in a daily amount of from 2.8 to 6.6mmol per day, over a period of at least 21 days. Also are provided are the compound of formula (l) for use in increasing mitophagy and/or autophagy, maintaining and/or improving musclefunction and administration as a dietary, nutritional and/or health supplement.
SKIN TREATMENT METHODS
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Page/Page column 29, (2018/09/28)
The invention provides a compound of formula (I) wherein: A, B, C, D, W, X, Y and Z are each independently selected from H and OH; or a salt thereof; for use in the treatment and/or prevention of a skin condition in a subject, wherein the compound of formula (I) or salt thereof is administered topically. The invention further provides topical compositons of a compound of formula (i) and processes for the preparation of said compositions.
