- Urolithins, intestinal microbial metabolites of pomegranate ~ellagitannins, exhibit potent antioxidant activity in a cell-based assay
-
Many health benefits of pomegranate products have been attributed to the potent antioxidant action of their tannin components, mainly punicalagins and ellagic acid. While moving through the intestines, ellagitannins are metabolized by gut bacteria into urolithins that readily enter systemic circulation. In this study, the antioxidant properties of seven urolithin derivatives were evaluated in a cell-based assay. This method is biologically more relevant because it reflects bioavailability of the test compound to the cells, and the antioxidant action Is determined in the cellular environment. Our results showed that the antioxidant activity of urolithins was correlated with the number of hydroxy groups as well as the lipophilicity of the molecule. The most potent antioxidants are urolithins C and D with IC50 values of 0.16 and 0.33 μM, respectively, when compared to IC50 values of 1.1 and 1.4 μM of the parent ellagic acid and punicalagins, respectively. The dihydroxylated urolithin A showed weaker antioxidant activity, with an IC 50 value 13.6 μM, however, the potency was within the range of urolithin A plasma concentrations. Therefore, products of the intestinal microbial transformation of pomegranate ellagitannins may account for systemic antioxidant effects.
- Dobroslawa, Bialonska,Kasimsetty, Sashi G.,Khan, Shabana I.,Daneel, Ferreira
-
-
Read Online
- Urolithin C, a gut metabolite of ellagic acid, induces apoptosis in PC12 cells through a mitochondria-mediated pathway
-
Urolithins (Uros), metabolites of ellagitannins (ET) and ellagic acid (EA) produced by gut microbiota, showed better bioavailability and extensive bioactivity, and were considered as the active compounds responsible for the health benefits exerted by ET-containing foodstuffs. Here, we chemically synthesized three Uros including Uros A, B, and C and compared their anti-proliferative activities with that of EA in PC12 cells. MTT assay showed that EA significantly promoted, while Uros significantly inhibited the proliferation of PC12 cells, among which UroC showed the strongest anti-proliferation. UroC treatment actively increased the lactate dehydrogenase (LDH) release and lipid peroxidation malondialdehyde (MDA), stimulated reactive oxygen species (ROS) formation and mitochondrial membrane depolarization, and caused calcium dyshomeostasis. Furthermore, flow cytometry analysis showed that UroC treatment induced apoptosis and S phase cell cycle arrest with increasing UroC concentrations. Consequently, UroC also induced imbalance in the Bcl-2/Bax ratio, which triggered the caspase cascade, thereby shifting the balance in favor of apoptosis, as evidenced by western blotting and real-time PCR. These observations indicated that UroC possessed significantly different anti-proliferation activities from EA, and actively induced cell apoptosis through a mitochondria-mediated pathway.
- Yin, Peipei,Zhang, Jianwei,Yan, Linlin,Yang, Lingguang,Sun, Liwei,Shi, Lingling,Ma, Chao,Liu, Yujun
-
-
Read Online
- Urolithin as a Converging Scaffold Linking Ellagic acid and Coumarin Analogues: Design of Potent Protein Kinase CK2 Inhibitors
-
Casein kinase2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (Ki=20nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, Ki=60nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithinA as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a Ki value of 7nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. Two become one: Comparing the crystallographic binding modes of ellagic acid (red) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC; blue), an X-ray structure-driven merging approach to the design of novel casein kinase2 (CK2) inhibitors was taken. Using this strategy, a potent and selective urolithin derivative, 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one was identified, which exhibits a Ki value of 7nM against CK2.
- Cozza, Giorgio,Gianoncelli, Alessandra,Bonvini, Paolo,Zorzi, Elisa,Pasquale, Riccardo,Rosolen, Angelo,Pinna, Lorenzo A.,Meggio, Flavio,Zagotto, Giuseppe,Moro, Stefano
-
-
Read Online
- Gut Microbiota conversion of dietary ellagic acid into bioactive phytoceutical urolithin a inhibits heme peroxidases
-
Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to interindividual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical- based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunitymicrobiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiotamediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.
- Saha, Piu,Yeoh, Beng San,Singh, Rajbir,Chandrasekar, Bhargavi,Vemula, Praveen Kumar,Haribabu, Bodduluri,Vijay-Kumar, Matam,Jala, Venkatakrishna R.
-
-
Read Online
- Urolithin and reduced urolithin derivatives as potent inhibitors of tyrosinase and melanogenesis: Importance of the 4-substituted resorcinol moiety
-
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.
- 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
-
-
- Urolithin A and B Derivatives as ON-OFF Selective Fluorescent Sensors for Iron(III)
-
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.
- Fallah, Amirhossein,Noshadi, Bahareh,Gazi, Mustafa,Gülcan, Hayrettin Ozan
-
p. 113 - 120
(2020/01/06)
-
- Synthesis, Characterization, Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs
-
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.
- Noshadi, Bahareh,Ercetin, Tugba,Luise, Chiara,Yuksel, Mine Yarim,Sippl, Wolfgang,Sahin, Mustafa Fethi,Gazi, Mustafa,Gulcan, Hayrettin Ozan
-
-
- Synthetic method of urolithin A
-
The invention discloses a synthetic method of urolithin A. The synthetic method comprises the steps of coupling, primary protective group removal, sulfonylation, carboxylation-lactonization, secondaryprotective group removal and the like. The method provided by the invention is a novel method for synthesizing urolithin A, the raw material is cheap and easy to obtain, the used reaction reagent issmall in environmental pollution and simple in route, and the method can be used for large-scale preparation of urolithin A.
- -
-
-
- Urolithins as immune response enhancers
-
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.
- -
-
Page/Page column 30-31
(2020/11/23)
-
- UROLITHINS-CONTAINING AQUEOUS SOLUTION, DRIED SOLID COMPOSITION THEREOF AND PRODUCTION METHOD THEREFOR, AND UROLITHINS STABILIZING METHOD
-
A urolithin-containing aqueous solution containing urolithin and collagen, a dried solid composition thereof, methods for producing these, and a stabilization method for urolithin.
- -
-
Paragraph 0125-0126
(2019/02/19)
-
- PROCESS-SCALE SYNTHESIS OF UROLITHIN A
-
Disclosed are methods for preparing a salt of urolithin A and, in turn, urolithin A. The methods are advantageous for the large-scale preparation of urolithin A or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0058-0159
(2019/09/06)
-
- METHODS FOR IMPROVING MITOPHAGY IN SUBJECTS
-
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.
- -
-
Page/Page column 52
(2018/09/28)
-
- METHODS FOR IMPROVING MITOPHAGY IN SUBJECTS
-
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.
- -
-
Page/Page column 54-55
(2018/09/28)
-
- SKIN TREATMENT METHODS
-
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.
- -
-
Page/Page column 29; 30
(2018/09/28)
-
- [...] containing, anti-wrinkle agents, collagen, MMP-a 1 production inhibitor, and elastase activity inhibitor (by machine translation)
-
[A] containing [...], anti-wrinkle agents, collagen, MMP-a 1 production inhibitor, and elastase activity-inhibiting agent. (1) represented by the general formula [a] [...] containing anti-wrinkle agent. (In the formula, R1, R2, R3, R4, R5, R6 and is, respectively, a hydroxyl group, a hydrogen atom or methoxy group, which, R1, R2, R3, R4, R5, R6 and one or more of the hydroxyl groups in 1. )Figure 1 [drawing] (by machine translation)
- -
-
Paragraph 0084
(2017/04/07)
-
- A light aging inhibitor [...] (by machine translation)
-
[A] suppressing effect for new uses of photoaging [...] aging inhibitor. (1) represented by the general formula [a] [...] containing light-aging inhibitor. (In the formula, R1, R2, R3, R4, R5, R6 and is, respectively, a hydroxyl group, a hydrogen atom or methoxy group, which, R1, R2, R3, R4, R5, R6 and one or more of the hydroxyl groups in 1. )Figure 1 [drawing] (by machine translation)
- -
-
Paragraph 0054
(2017/05/23)
-
- HYALURONIC ACID PRODUCTION PROMOTER CONTAINING UROLITHINS
-
PROBLEM TO BE SOLVED: To provide novel hyaluronic acid production promoter containing urolithins. SOLUTION: The hyaluronic acid production promoters contain urolithins represented by the general formula (1) in the figure. (In the formula, R1, R2, R3, R4, R5 and R6 each represent a hydroxy group, hydrogen atom or methoxy group, provided that one or more of R1, R2, R3, R4, R5 and R6 are hydroxy groups.) SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2017,JPOandINPIT
- -
-
Paragraph 0061
(2017/08/02)
-
- COMPOSITIONS COMPRISING AN UROLITHIN COMPOUND
-
The invention provides compositions comprising a source of protein and a urolithin. The invention also provides uses and methods associated with, or making use of the compositions, such as a medicament, dietary supplement, functional food or medical food and in the treatment and/or prophylaxis of a muscle-related pathological condition. The invention also provides kits comprising urolithin and protein.
- -
-
Page/Page column 20; 21
(2017/03/21)
-
- COMPOSITIONS COMPRISING UROLITHIN COMPOUNDS
-
The invention provides compositions comprising a medium chain triglyceride and a urolithin. The invention also provides uses and methods associated with, or making use of the compositions,such as a medicament, dietary supplement, functional food or medical food and in the treatment and/or prophylaxis of a muscle-related pathological condition.
- -
-
Page/Page column 21
(2017/03/21)
-
- COMPOSITIONS COMPRISING NICOTINAMIDE RIBOSIDE AND A UROLITHIN
-
A composition comprising: a)nicotinamide riboside and b)a urolithin which is a compound of formula (I) or a salt thereof: Formula (I) wherein: A, B, C and D are each independently selected from H and OH; W, X and Y are each independently selected from H and OH; and Z is selected from H and OH. The compositions are useful as medicaments, for example for treating muscle-related pathological conditions, neurodegenerative diseases, and/or mitochondrial diseases and as dietary supplements, functional foods and beverages, and specialised nutrition or medical foods.
- -
-
Page/Page column 25
(2017/07/14)
-
- ANTIGLYCATION AGENTS CONTAINING UROLITHINS
-
PROBLEM TO BE SOLVED: To provide antiglycation agents containing urolithins being antiglycation substances. SOLUTION: Antiglycation agents contain urolithins represented by the general formula (1) in the figure. (In the formula, R1, R2, R3, R4, R5 and R6 each represent a hydroxy group, hydrogen atom or methoxy group, provided that one or more of R1, R2, R3, R4, R5 and R6 are hydroxy groups.) SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2017,JPOandINPIT
- -
-
Paragraph 0056
(2017/06/02)
-
- HAIR TONICS CONTAINING UROLITHINS, AND 5α-REDUCTASE ACTIVITY INHIBITORS CONTAINING UROLITHINS
-
PROBLEM TO BE SOLVED: To provide novel hair tonics containing urolithins, and novel 5α-reductase activity inhibitors containing urolithins. SOLUTION: The invention provides hair tonics containing urolithins, and 5α-reductase activity inhibitors containing urolithins. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2017,JPOandINPIT
- -
-
Paragraph 0063
(2018/08/30)
-
- COMPOSITIONS COMPRISING UROLITHINS AND USES THEREOF FOR THE STIMULATION OF INSULIN SECRETION
-
The present invention relates to a composition comprising urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion, and to the use of a compound chosen among urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, intended for the stimulation of insulin secretion. The present invention also relates to a composition comprising an effective amount of urolithin B, urolithin C, urolithin D, or a combination thereof, for the treatment or the prevention of diabetes mellitus, and in particular for the treatment or the prevention of type 2 diabetes, and to the use of a compound chosen among urolithin B, urolithin C, urolithin D, and a combination thereof, intended for the treatment or the prevention of diabetes mellitus, and in particular of type 2 diabetes.
- -
-
Page/Page column 20
(2015/05/05)
-
- Compositions comprising urolithins and uses thereof for the stimulation of insulin secretion
-
The present invention relates to a composition comprising an effective amount of urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion, and to the use of a compound chosen among urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion. The present invention also relates to a composition comprising an effective amount of urolithin B, urolithin C, urolithin D, or a combination thereof, for the treatment or the prevention of diabetes mellitus, and to the use of a compound chosen among urolithin B, urolithin C, urolithin D, and a combination thereof, for the treatment or the prevention of diabetes mellitus.
- -
-
Paragraph 0069
(2015/05/05)
-
- PROCESS-SCALE SYNTHESIS OF UROLITHINS
-
Disclosed is a method of preparing a urolithin, or an intermediate or analog thereof, having a dibenzo[b,d]pyran-6-one core. The method is especially advantageous for the large-scale preparation of urolithins or intermediates or analogs thereof. The method may optionally include the preparation of a urolithin, or an intermediate or analog thereof, as a pharmaceutically acceptable salt.
- -
-
Page/Page column 40; 41; 42; 43; 44; 45
(2015/07/15)
-
- ENHANCING AUTOPHAGY OR INCREASING LONGEVITY BY ADMINISTRATION OF UROLITHINS OR PRECURSORS THEREOF
-
Disclosed are methods, compounds, and compositions useful for increasing autophagy and promoting longevity. The methods, compounds, and compositions relate to urolithins and urolithin precursors and use thereof. Certain urolithins are represented by Formula I, while certain urolithin precursors are represented by Formula IV. The urolithin may be urolithin A, urolithin B, urolithin C, or urolithin D. The urolithin precursor may be ellagic acid or an ellagitannin. The methods include in vivo, ex vivo, and in vitro uses of the compounds and compositions.
- -
-
-
- Cu(I)-mediated lactone formation in subcritical water: A benign synthesis of benzopyranones and urolithins A-C
-
Benzopyranones were successfully synthesized using Cu(I)-mediated C-O bond formation in subcritical water. A number of benzopyranone derivatives including polymethoxy benzopyranones, benzopyranopyridones, chromenoindolones, and furochromenones were synthesized in satisfactory yield. This methodology was further applied to synthesize the intestinal microbial metabolites, urolithins A, B, and C, which were found to exhibit potent antioxidant activity.
- Nealmongkol, Prattya,Tangdenpaisal, Kassrin,Sitthimonchai, Somkid,Ruchirawat, Somsak,Thasana, Nopporn
-
p. 9277 - 9283
(2013/10/01)
-
- Identification of urinary and intestinal bacterial metabolites of ellagitannin geraniin in rats
-
Hydrolyzable tannins, including ellagitannins, occur in foods such as berries and nuts. Various biological activities, including antioxidant, antiviral, and antitumor activities, have been noted and reported for ellagitannins, but the absorption and metabolism of purified ellagitannins are poorly understood. We describe herein the characterization of urinary and intestinal microbial metabolites in rats after the ingestion of ellagitannins. Urine samples were collected after oral administration of ellagitannins such as geraniin (1), corilagin (2), and their related polyphenols. The suspension of rat intestinal microflora was anaerobically incubated with ellagitannins. Each sample was separated by column chromatography and/or preparative HPLC to give seven metabolites, M1-M7. The structures of these metabolites were determined on the basis of spectroscopic data and chemical evidence. These compounds, except for M1, were characterized as ellagitannin metabolites for the first time. Furthermore, among four major metabolites (M1-M4) in urine, M2 showed an antioxidant activity comparable to intact geraniin and related polyphenols.
- Ito, Hideyuki,Iguchi, Ayumu,Hatano, Tsutomu
-
experimental part
p. 393 - 400
(2009/04/10)
-
- Mitochondria-targeted antioxidants
-
The present invention relates to a pharmaceutical or veterinary or nutritional or personal care composition comprising coenzyme Q10 (CoQ10), reduced CoQ10, or mixtures thereof and oxygenated dibenzo-α-pyrone or an amino acyl ester thereof. The composition of the present invention is able to support and/or provide therapy to individuals at risk and/or under treatment for dysfunctions of energy metabolism, and specifically, for mitochondrial diseases.
- -
-
-
- Compositions of stable bioactive metabolites of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids
-
An invention that adduces cogent evidence to establish that oxygenated dibenzo-α-pyrones (DBPs and their conjugates), the major bioactives of shilajit (Ayurvedic vitalizer), have their origin, at least partly, in EPA and DHA. Earlier research has shown that, in mammals, C-20 PUFAs are metabolized by oxygenases and other enzymes to produce short-lived prostaglandins, leukotrienes and thromboxanes that bind to specific G-protein-coupled receptors and signal cellular responses, e.g., inflammation, vasodilation, blood pressure, pain etc. But never before it was suggested/shown that C20:5n-3 (and C22:6 n-3) PUFAs, e.g., EPA (and DHA), are transformed into stable aromatic metabolites, DBPs, which elicit a large array of bioactivities in the producer organisms and also control the synthesis and metabolism of arachidonate-derived prostaglandins. The major beneficial effects attributed to EPA and DHA are now found to be largely contributed by DBPs and their aminoacyl conjugates and the dibenzo-α-pyrone-chromoproteins (DCPs). Because of the highly unstable nature of EPA and DHA, when administered, they are metabolized into a large array of uncontrolled products, several of which are systemically undesirable. By contrast, DBPs, because of their stability, perform the biological response modifier (BRM) functions in a directed and sustained way. Many of the biological effects of DBPs described in this invention, were earlier attributed to EPA and DHA,—the precursors of DBPs.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- Synthesis and biological activities of some new dibenzopyranones and dibenzopyrans: Search for potential oestrogen receptor agonists and antagonists
-
Continuing our search for newer oestrogen agonists or antagonists and extending our work on the exploration of benzopyran related compounds, some new tricyclic molecules bridged between the active molecules of 3,4-diaryl chroman and 2,3-diaryl benzopyrans have been synthesised. Structural modifications at different positions with elements known to impart agonist or antagonist activities have been carried out to prepare the desired molecules. The target compounds were screened for their anti-osteoporotic (agonist) and anti-uterotrophic (antagonist) activities and were found to be moderately active.
- Pandey, Jaya,Jha, Ashok K.,Hajela
-
p. 2239 - 2249
(2007/10/03)
-
- Sequential Directed Ortho Metalation-Boronic Acid Cross-Coupling Reactions. A General Regiospecific Route to Oxygenated Dibenzopyran-6-ones Related to Ellagic Acid
-
A general regiospecific synthesis of dibenzopyran-6-one derivatives 1a,c and 8a-i related to ellagic acid is described (Scheme I, Table I).The sequence involves directed ortho metalation-boronation of benzamides 4 to give the arylboronic acids 5, which, upon palladium-catalyzed cross-coupling with alkoxybromobenzenes 6 leads to the biphenylamides 7.BBr3 demethylation followed by acid-catalyzed cyclization affords pyranone 8.In this manner, the naturally occurring dibenzopyranones 1a, autumnariol (1c), and the heterocyclic analogue 13 (Scheme III) were efficiently prepared.
- Alo, B. I.,Kandil, A.,Patil, P. A.,Sharp, M. J.,Siddiqui, M. A.,et al.
-
p. 3763 - 3768
(2007/10/02)
-
