- Preparation, characterizations and anti-pollutant activity of 7,3′,4′-trihydroxyisoflavone nanoparticles in particulate matter-induced HaCaT keratinocytes
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Background: 7,3′,4′-Trihydroxyisoflavone (734THI), a secondary metabolite derived from daidzein in soybean, possesses several biological activities, including antioxidant, skin whitening and anti-atopic dermatitis properties, but the poor aqueous solubility of 734THI has limited its application in medicine and cosmetic industry. Methods: The aim of the present study was to improve the physicochemical properties of 734THI using planetary ball mill preparation under a solvent-free process to improve its solubility and anti-pollutant activity. Results: 734THI nanoparticle powder (734THIN) was successfully prepared by the planetary ball mill technique using polyvinylpyrrolidone K30 as the excipient. 734THIN effectively increased the aqueous solubility and cellular uptake of 734THI by improving its physicochemical properties, including particle size reduction, crystalline–amorphous transformation and intermolecular hydrogen bonding with polyvinylpyrrolidone K30. In addition, 734THIN inhibited the overexpression of COX-2 and MMP-9 by downregulating MAPK pathway signaling in particulate matter-exposed HaCaT keratinocytes, while raw 734THI in PBS with low aqueous solubility did not show any anti-inflammatory or antiaging activity. Conclusion: 734THIN may be used as an additive in anti-pollutant skin care products for preventing particulate matter-induced inflammation and aging in skin.
- Huang, Pao-Hsien,Tseng, Chih-Hua,Lin, Chia-Yu,Lee, Chiang-Wen,Yen, Feng-Lin
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- Biotransformation of isoflavone using enzymatic reactions
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The roles of cytochrome P450 monooxygenases (CYPs) from Streptomyces spp. which are called the treasure islands for natural products for medicine and antibiotics are not well understood. Substrate specificity studies on CYPs may give a solution for elucidation of their roles. Based on homology sequence information, the CYP105D7 of a soluble cytochrome P450 known as heme protein from Streptomyces avermitilis MA4680 was expressed using the T7 promoter of the bacterial expression vector pET24ma, over-expressed in Escherichia coli system and characterized. An engineered whole cell system for daidzein hydroxylation was constructed using an exogenous electron transport system from ferredoxin reductase (PdR) and ferredoxin (Pdx). Also, an in vitro reaction study showed the purified CYP105D7 enzyme, using NADH-dependent-reducing equivalents of a redox partner from Pseudomonas putida, hydroxylated daidzein at the 3' position of the B ring to produce 7,3,'4' trihydroxyisoflavone. The hydroxylated position was confirmed by GC-MS analysis. The turnover number of the enzyme was 0.69 μmol 7,3,'4'-trihydroxyisoflavone produced per μmol P450 per min. This enzyme CYP105D7 represents a novel type of 3'-hydroxylase for daidzein hydroxylation. A P450 inhibitor such as coumarin significantly (ca.98%) inhibited the daidzein hydroxylation activity.
- Roh, Changhyun
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- The effectiveness of synthetic methoxylated isoflavones in delivering to the skin and alleviating psoriasiform lesions via topical absorption
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This study was conducted to appraise the possible potential of synthetic isoflavones (SIFs) on psoriasis treatment. A practical and easy-to-operate approach was employed in synthesizing a series of SIFs, considering that acquiring flavonoids from natural resources is usually expensive, time-consuming, and non-eco-friendly. Seven SIFs derived from daidzein were produced with differences in the location of the hydroxyl groups and degree of methoxylation. The in vitro and in vivo skin absorption of topically applied SIFs was estimated. Further, keratinocytes (HaCaT) were employed as the model to investigate the anti-inflammatory activity of the isoflavones. The lipophilicity was increased from SIF-1 to ?7. Noteworthily, there was a parabolic relationship between lipophilicity and skin absorption, with SIF-5 (4′,7-dihydroxyisoflavone, daidzein) and SIF-6 (7-hydroxy-3′,4′-dimethoxyisoflavone, cladrin) demonstrating the highest retention in pig skin. The methoxylated isoflavone SIF-5 showed the greatest permeation into barrier-deficient skin among the compounds tested, with a 6- and 8-fold increase after lipid and protein removal. The cell-based study exhibited the capability of SIFs to restrain the overexpressed IL-6, IL-8, and CXCL1 in stimulated HaCaT. The therapeutic index (TI) predicted the potential candidates of SIF-5 and SIF-6 for topical application to treat psoriatic inflammation. The imiquimod (IMQ)-driven psoriasiform murine model manifested the inhibition of hyperplasia and immune cell infiltration by topically administered SIF-5 and SIF-6. The epidermal thickness of IMQ-treated skin was decreased from 172 to 40 μm by both isoflavones. This effect was comparable with that of betamethasone, the positive control. The topical treatment of SIF-6 significantly reduced cytokine/chemokine upregulation by IMQ. The methoxylated isoflavone with dramatic anti-inflammatory activity is promising for the development of an antipsoriatic agent.
- Aljuffali, Ibrahim A.,Fang, Jia-You,Huang, Jhao-Rong,Lin, Chwan-Fwu,Tseng, Chih-Hua,Yang, Sien-Hung
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- Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid β plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation
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In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid β (Aβ) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure–activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aβ aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aβ and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aβ42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.
- Son, Seung Hwan,Do, Ji Min,Yoo, Ji-Na,Lee, Hyun Woo,Kim, Nam Kwon,Yoo, Hyung-Seok,Gee, Min Sung,Kim, Jong-Ho,Seong, Ji Hye,Inn, Kyung-Soo,Seo, Min-Duk,Lee, Jong Kil,Kim, Nam-Jung
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- Natural Isoflavones and Semisynthetic Derivatives as Pancreatic Lipase Inhibitors
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Obesity, now widespread all over the world, is frequently associated with some chronic diseases. Thus, there is a growing interest in the prevention and treatment of obesity. To date, the only antiobesity drug is orlistat, a natural product-derived pancreatic lipase (PL) inhibitor with some undesired side effects. In the last decades, many natural compounds or derivatives have been evaluated as potential PL inhibitors, and natural polyphenols are among the most promising for possible exploitation as antiobesity agents. However, few studies have been devoted to isoflavones. In this work, we report a study on the PL inhibitory properties of a small library of semisynthetic isoflavone derivatives together with the natural leads daidzein (1), genistein (2), and formononetin (3). In vitro lipase inhibition assay showed that 2 is the most promising PL inhibitor. Among synthetic isoflavones, the hydroxylated and brominated derivatives were more potent than their natural leads. Detailed studies through fluorescence measurements and kinetics of lipase inhibition showed that 2 and the bromoderivatives 10 and 11 have the greatest affinity for PL. Docking studies corroborated these findings highlighting the interactions between isoflavones and the enzyme, confirming that hydroxylation and bromination are useful modifications.
- Cardullo, Nunzio,Muccilli, Vera,Pulvirenti, Luana,Tringali, Corrado
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p. 654 - 665
(2021/04/02)
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- Synthesis method of 3 ', 4', 7-trihydroxy isoflavone
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The invention discloses a synthesis method of 3', 4', 7-trihydroxy isoflavone. The method comprises the steps that 4', 7-dimethoxyisoflavone and bromine are subjected to a mixed reaction in a dichloromethane medium to obtain 3'-bromo-4 ', 7-dimethoxyisoflavone, wherein the molar ratio of 4', 7-dimethoxyisoflavone to bromine is 1: 1.1-1.5, and the reaction temperature is 20-30 DEG C; the 3'-bromo-4', 7-dimethoxyisoflavone reacts with sodium methoxide under the action of cuprous salt to obtain 3', 4', 7-trimethoxyisoflavone; and the 3', 4', 7-trimethoxyisoflavone is demethylated to obtain the 3', 4', 7-trihydroxy isoflavone. Compared with the prior art, the method has the advantages of abundant sources of initial raw materials, mild reaction conditions, high selectivity and high yield, and is suitable for industrial production.
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Paragraph 0030-0031; 0041-0042
(2020/09/09)
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- Development of 3-alkyl-6-methoxy-7-hydroxy-chromones (AMHCs) from natural isoflavones, a new class of fluorescent scaffolds for biological imaging
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Starting from 7-hydroxyisoflavones, we developed a new class of fluorescent scaffolds, 3-alkyl-6-methoxy-7-hydroxy-chromones (AMHCs, MW ～ 205.19, λab ～ 350 nm, λem ～ 450 nm) via a trial and error process. AMHCs have the advantages of being a small molecular moiety, having strong fluorescence in basic buffers, reasonable solubility and stability, non-toxicity, and are conveniently linked to pharmacophores. AMHCs were successfully used in fluorescence microscopy imaging of cells and tissues. This journal is
- Miao, Jianzhuang,Cui, Huaqing,Jin, Jing,Lai, Fangfang,Wen, Hui,Zhang, Xiang,Ruda, Gian Filippo,Chen, Xiaoguang,Yin, Dali
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p. 881 - 884
(2015/02/19)
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- CATECHOL DERIVATIVES PREPARED BY USING TYROSINASE, METHOD FOR PREPARATION THEREOF, AND APPLICATION THEREOF
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The present invention refers to using tyrosinase and pyrocatechole type structural material technology and exclusively on the basis of the response in the biosynthesis of, melanocyte secondary oxidation reaction by effectively inhibiting, mono phenol type primary structural material optionally catalyst only complex induced a are defined.. The present invention refers to using the same variety of functional pyrocatechole type materials, with high productivity and. there is provided a technique for production yield. (by machine translation)
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Paragraph 0074; 0075; 0076; 0082; 0083
(2016/12/12)
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- A Versatile Microbial System for Biosynthesis of Novel Polyphenols with Altered Estrogen Receptor Binding Activity
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Isoflavonoids possess enormous potential for human health with potential impact on heart disease and cancer, and some display striking affinities for steroid receptors. Synthesized primarily by legumes, isoflavonoids are present in low and variable abundance within complex mixtures, complicating efforts to assess their clinical potential. To satisfy the need for controlled, efficient, and flexible biosynthesis of isoflavonoids, a three-enzyme system has been constructed in yeast that can convert natural and synthetic flavanones into their corresponding isoflavones in practical quantities. Based on the determination of the substrate requirements of isoflavone synthase, a series of natural and nonnatural isoflavones were prepared and their binding affinities for the human estrogen receptors (ERα and ERβ) were determined. Structure activity relationships are suggested based on changes to binding affinities related to small variations on the isoflavone structure.
- Chemler, Joseph A.,Lim, Chin Giaw,Daiss, John L.,Koffas, Mattheos A.G.
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experimental part
p. 392 - 401
(2011/06/28)
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- FLAVONOID PPAR AGONISTS
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The present invention relates to PPAR agonists, and their use in therapy including the treatment of disease. In particular, the invention relates to flavonoid compounds which are PPAR-gamma agonists and/or PPAR alpha/gamma dual agonists.
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Page/Page column 38; 72-73
(2009/04/25)
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- 7-Hydroxy-benzopyran-4-one derivatives: A novel pharmacophore of peroxisome proliferator-activated receptor α and -γ (PPARα and γ) dual agonists
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Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead PPAR ligands were identified from "natraceuticals" and synthetic analogues. In total, 77 molecules, including chalcones, flavones, flavanones, isoflavones, and pyrazole derivatives, were screened and structure-activity relationship studies of the dual agonists undertaken. Compounds 68, 70, 72, and 76 were identified as novel and potent dual PPARα and γ agonists. These novel molecules may have the potential to be the future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome. 2009 American Chemical Society.
- Matin, Azadeh,Gavande, Navnath,Kim, Moon S.,Yang, Nancy X.,Salam, Noeris K.,Hanrahan, Jane R.,Roubin, Rebecca H.,Hibbs, David E.
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experimental part
p. 6835 - 6850
(2010/04/04)
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- Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
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Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10') were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1- diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12-54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E-I) and their biphenyl-ketone derivatives (10E-H) also showed a high activity (ED50=50=26-32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3'-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10') by metabolism or biotransformation.
- Goto, Hideyuki,Terao, Yoshiyasu,Akai, Shuji
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experimental part
p. 346 - 360
(2009/12/27)
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- COMPOUNDS USEFUL FOR THE INHIBITION OF ALDH
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The present invention provides novel antidipsotropic compounds. The invention further provides methods of inhibiting ALDH-2 using the compounds described herein. Methods for modulating alcohol consumption, alcohol dependence and/or alcohol abuse by administering the compounds of the invention to an individual are also provided. The present invention further provides a rationale for designing additional novel antidipsotropic compounds.
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(2010/11/30)
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- Syntheses of Isoflavones and Isoflavone Glycosides, and Their Inhibitory Activity against Bovine Liver &β-Galactosidase
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To clarify the relationship between the structure and inhibitory action toward β-D-galactosidase (EC 3.2.1.21) of isoflavones and isoflavone glycosides, a number of polyhydroxyisoflavones, and the α-L-rhamnosides and β-L-quinovosides of daidzein and genistein were synthesized.Among the polyhydroxyisoflavones, 2',3',4',7-tetrahydroxyisoflavone showed the strongest inhibitory activity (Ki = 26 * 10-6 M).Among the glycosides, all the L-rhamnosides were strong inhibitors, of which genistein 4',7-di-O-α-L-rhamnoside was the strongest (Ki = 4.44 * 10-6 M), while all the isoflavone β-L-quinovosides were considerably weak or possessed no inhibition.
- Nishiyama, Kiyotoshi,Esaki, Sachiko,Deguchi, Ikuko,Sugiyama, Naoko,Kamiya, Shintaro
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p. 107 - 114
(2007/10/02)
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- HYDROBORATIONS: NEW SYNTHESIS OF PSEUDO-BAPTIGENIN, O-METHYL PSEUDO-BAPTIGENIN AND CABREUVIN.
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Application of hydroboration followed by chromic acid oxydation to 4-hydroxy 7-methoxy(3',4'-methylenedioxyphenyl) coumarin and 4-hydroxy 7-benzyloxy 3-(3',4'-methylenedioxyphenyl) coumarin forms the corresponding isoflavanones which are dehydrogenated into isoflavones.
- Kirkiacharian, B. Serge,Brion, Jean-Daniel,Gomis, Michel,Reynaud, Pierre
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p. 1929 - 1934
(2007/10/02)
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