- Enantioselective Synthesis of Isoflavanones and Pterocarpans through a RuII-Catalyzed ATH-DKR of Isoflavones
-
Noyori-Ikariya RuII complexes promoted the one-pot C=C/C=O bonds reduction of isoflavones using sodium formate as the hydrogen source through Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution (ATH-DKR). Due to the neutral conditions employed, isoflavones with different substituents at the 2’-position of B-ring (H, OH, OMe and Br) were successfully reduced. Ten cis-3-phenylchroman-4-ols were selectively obtained (>20 : 1 dr) in good yields (up to 86 %) and excellent enantioselectivities (up to >99 : 1 er). The synthetic applications of these chiral compounds were also demonstrated. Enantioenriched isoflavanones were obtained under mild metal-free oxidation of the cis-3-phenylchroman-4-ols while pterocarpans were synthesized by two strategies: an acid-catalyzed cyclization and a novel approach based on a Pd-catalyzed C?O intramolecular cross-coupling reaction.
- Caleffi, Guilherme S.,Costa, Paulo R. R.,Costa-Júnior, Paulo C. T.,Gaspar, Francisco V.
-
p. 5097 - 5108
(2021/10/20)
-
- A Concise Approach to Oxo-Dehydrorotenoid by Direct Lactonization and the Total Syntheses of Stemonone, Rotenonone, 6-Oxo-dehydroelliptone, and 6-Oxo-6a,12a-dehydrodeguelin
-
An approach to construct the oxo-dehydrorotenoids via direct lactonization of isoflavone-2-carboxylic acids is reported. The present reaction proceeds smoothly with good substrate scope and an operationally simple protocol. The application of this method
- Boonsombat, Jutatip,Thongnest, Sanit,Ruchirawat, Somsak
-
supporting information
p. 2971 - 2983
(2019/03/27)
-
- 3, 9-di-O-substituted coumestrols incorporating basic amine side chains act as novel apoptosis inducers with improved pharmacological selectivity
-
There is much interest in the use of phytoestrogens such as coumestrol in breast cancer intervention due to their antiestrogenic activity and multiple modes of tumor cell death. However, the clear beneficial effects of naturally occurring estrogen mimetic coumestrol remain controversial due to experimental evidence that it has been shown to stimulate MCF-7 cell proliferation via agonist effect on estrogen receptor at low concentration. Herein, to disconnect the ER interaction and apoptosis-specific mechanism of coumestrol, various 3, 9-di-O-substituted coumestrols (7a-7e) and their furan ring-opened analogs (5a-5e) were synthesized and assessed for antiproliferative properties. Attachment of a dimethylamine-containing side chain to 3-O of coumestrol led to the most promising compound 7e with improved antiproliferative activity (1.7-fold increase) against MCF-7 cells, decreased estrogen activity (>20 times weaker ERα binder) and a novel action to induce apoptosis. Mechanistic studies revealed that 7e is a tubulin polymerization inhibitor, which could arrest cell cycle at G2/M phase and induce apoptosis along with the decrease of mitochondrial membrane potential. In summary, such subtle modifications to the 3, 9-di-hydroxyl groups of coumestrol allow the generation of a novel apoptosis inducer with distinct pharmacological properties, providing an excellent starting point to future development of novel tumor-vascular disrupting agents targeting tubulin.
- Luo, Guoshun,Tang, Zhengpu,Li, Xinyu,Hou, Qiangqiang,Chen, Yu,Lao, Kejing,Xiang, Hua
-
p. 140 - 151
(2019/01/08)
-
- Design, synthesis, and biological evaluation of truncated deguelin derivatives as Hsp90 inhibitors
-
A series of novel B[sbnd] and C-rings truncated deguelin derivatives have been designed and synthesized in the present study as heat shock protein 90 (Hsp90) inhibitors. The synthesized compounds exhibited micromolar antiproliferative potency toward a pan
- Yao, Hong,Xu, Feijie,Wang, Guangyu,Xie, Shaowen,Li, Wenlong,Yao, Hequan,Ma, Cong,Zhu, Zheying,Xu, Jinyi,Xu, Shengtao
-
p. 485 - 498
(2019/02/24)
-
- A Direct Synthesis of 2-(ω-Carboxyalkyl)isoflavones from ortho-Hydroxylated Deoxybenzoins
-
As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin-modified isoflavones to identify potential biological targets, and we selected the C-2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base-catalyzed condensation of 2,4-dihydroxy-substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene led to an efficient synthesis of the desired 2-(ω-carboxyalkyl)isoflavones with functional groups at C-5, 6 and 7 and with various substituents in the C-3 phenyl group.
- Mrug, Galyna P.,Demydchuk, Bohdan A.,Bondarenko, Svitlana P.,Sviripa, Vitaliy M.,Wyrebek, Przemyslaw,Mohler, James L.,Fiandalo, Michael V.,Liu, Chunming,Frasinyuk, Mykhaylo S.,Watt, David S.
-
supporting information
p. 5460 - 5463
(2018/10/20)
-
- Synthesis of structurally diverse biflavonoids
-
Synthetic biflavonoids are associated with interesting biological activities, yet they remain poorly explored within drug discovery. Recent years have witnessed a growing interest in synthetic approaches that can provide access to structurally novel biflavonoids so that the biological usefulness of this compound class can be more fully investigated. Herein, we report upon the exploration of strategies based around Suzuki-Miyaura cross-coupling and alcohol methylenation for the synthesis of two classes of biflavonoids: (i) rare ‘hybrid’ derivatives containing flavonoid monomers belonging to different subclasses, and (ii) homodimeric compounds in which the two flavonoid monomers are linked by a methylenedioxy group. Application of these strategies enabled the preparation of a structurally diverse collection of novel biflavonoids from readily-available starting materials, thereby facilitating the probing of uncharted regions of biologically interesting chemical space.
- Sum, Tze Jing,Sum, Tze Han,Galloway, Warren R.J.D.,Twigg, David G.,Ciardiello, Joe J.,Spring, David R.
-
supporting information
p. 5089 - 5101
(2018/05/23)
-
- Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities
-
Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.
- Qiu, Rongmao,Luo, Guoshun,Cai, Xuerong,Liu, Linyi,Chen, Mingqi,Chen, Deying,You, Qidong,Xiang, Hua
-
supporting information
p. 3726 - 3730
(2018/10/20)
-
- CYTISINE-LINKED ISOFLAVONOID ANTINEOPLASTIC AGENTS FOR THE TREATMENT OF CANCER
-
Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example.
- -
-
Paragraph 0063; 0065
(2019/01/04)
-
- Novel isoflavone derivative, preparation method therefor and medicinal use of novel isoflavone derivative
-
The invention relates to the field of pharmaceutical chemistry, relates to an isoflavone derivative, a preparation method therefor and medicinal use of the novel isoflavone derivative and particularlyrelates to isoflavone derivatives represented by a general formula (I) shown in the description, preparation methods therefor, pharmaceutical compositions containing these compounds and medicinal useof the isoflavone derivatives and the pharmaceutical compositions, particularly use of drugs for preventing or treating hyperlipidemia, type II diabetes, atherosclerosis and non-alcoholic fatty hepatitis.
- -
-
Paragraph 0054-0055; 0059-0060
(2018/07/30)
-
- Design, synthesis and biological evaluation of novel 3-substituted 4-anilino-coumarin derivatives as antitumor agents
-
Various 3-substituted 4-anilino-coumarin derivatives have been designed, synthesized and their anti-proliferative properties have been studied. The in vitro cytotoxicity screening was performed against MCF-7, HepG2, HCT116 and Panc-1 cancer cell lines by MTT assay. Most of the synthesized compounds exhibited comparable anti-proliferative activity to the positive control 5-Fluorouracil against these four tested cancer cell lines. Among the different substituents at C-3 position of coumarin scaffold, 3-trifluoroacetyl group showed the most promising results. Especially, compounds 33d (IC50?=?16.57, 5.45, 4.42 and 5.16?μM) and 33e (IC50?=?20.14, 6.71, 4.62 and 5.62?μM) showed excellent anti-proliferative activities on MCF-7, HepG2, HCT116 and Panc-1 cell lines respectively. In addition, cell cycle analysis and apoptosis activation revealed that 33d induced G2/M phase arrest and apoptosis in MCF-7 cells in a dose-dependent manner. Low toxicity of compounds 33d and 33e was observed against human umbilical vein endothelial cells (HUVECs), suggesting their acceptable safety profiles in normal cells. Furthermore, the results of in silico ADME studies indicated that both 33d and 33e exhibited good pharmacokinetic properties.
- Luo, Guoshun,Muyaba, Moses,Lyu, Weiting,Tang, Zhichao,Zhao, Ruheng,Xu, Qian,You, Qidong,Xiang, Hua
-
supporting information
p. 867 - 874
(2017/02/18)
-
- Coumadin female phenol split-ring analogue and its medical use
-
The invention relates to the field of pharmaceutical chemistry, in particular to a coumestrol open-ring analogue with structures as shown in general formulae I and II and a medical application thereof, especially an application to the preparation of drugs as angiogenesis inhibition and vascular disruption agents.
- -
-
Paragraph 0027-0029
(2017/10/06)
-
- Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)
-
Cytisine-linked isoflavonoids (CLIFs) inhibited PC-3 prostate and LS174T colon cancer cell proliferation by inhibiting a peroxisomal bifunctional enzyme. A pull-down assay using a biologically active, biotin-modified CLIF identified the target of these agents as the bifunctional peroxisomal enzyme, hydroxysteroid 17β-dehydrogenase-4 (HSD17B4). Additional studies with truncated versions of HSD17B4 established that CLIFs specifically bind the C-terminus of HSD17B4 and selectively inhibited the enoyl CoA hydratase but not the d-3-hydroxyacyl CoA dehydrogenase activity. HSD17B4 was overexpressed in prostate and colon cancer tissues, knocking down HSD17B4 inhibited cancer cell proliferation, suggesting that HSD17B4 is a potential biomarker and drug target and that CLIFs are potential probes or therapeutic agents for these cancers.
- Frasinyuk, Mykhaylo S.,Zhang, Wen,Wyrebek, Przemyslaw,Yu, Tianxin,Xu, Xuehe,Sviripa, Vitaliy M.,Bondarenko, Svitlana P.,Xie, Yanqi,Ngo, Huy X.,Morris, Andrew J.,Mohler, James L.,Fiandalo, Michael V.,Watt, David S.,Liu, Chunming
-
supporting information
p. 7623 - 7629
(2017/09/27)
-
- Preparation method of 2,4-dyhydroxyl-4-methoxy deoxidization benzoin
-
The invention discloses a preparation method of 2,4-dyhydroxyl-4-methoxy deoxidization benzoin. The preparation method comprises the following steps: (1) adding resorcinol, zinc chloride and para-methoxyphenylacetic acid into a drying container, vacuumizi
- -
-
Paragraph 0013; 0014; 0015; 0016- 0024
(2017/04/28)
-
- Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases
-
To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.
- Vo, Chau D.,Shebert, Hanna L.,Zikovich, Shannon,Dryer, Rebecca A.,Huang, Tony P.,Moran, Lindsey J.,Cho, Juno,Wassarman, Douglas R.,Falahee, Bryn E.,Young, Peter D.,Gu, Garrick H.,Heinl, James F.,Hammond, John W.,Jackvony, Taylor N.,Frederick, Thomas E.,Blair, Jimmy A.
-
supporting information
p. 5235 - 5244
(2017/11/01)
-
- 3-aryl-4-arylamine-coumarin derivative and preparing method and medical application thereof
-
The invention relates to the field of medicinal chemistry, in particular to a series of 3-aryl-4-arylamine-coumarin derivatives and a preparing method and medical application thereof, especially medicine applied to curing cancer like breast cancer. A structural formula of a 3-aryl-4-arylamine-coumarin derivative compound is as follow, and definitions of all radical groups in the formula are shown in instructions in details. The structural formula is shown in the specification.
- -
-
Paragraph 0094; 0095
(2016/10/31)
-
- Design and synthesis of 3-arylbenzopyran based non-steroidal vitamin-D3 mimics as osteogenic agents
-
3-Arylbenzopyran based non-steroidal osteogenic agents have been explored as structural templates of estrogen and vitamin-D3. The target molecules 18a-c, 19a-c, 26a-c, 27a-c and intermediates 17a-c and 25a-c were studied for their osteogenic activity in an osteoblast differentiation assay in vitro using mouse calvarial osteoblast cells. Compounds 25c, 26b, 27b and 27c effectively increased ALP activity at 1 pM concentration compared to the untreated cells. The active compounds were devoid of inherent toxicity at 1 pM concentration in osteoblast cells. The most active compound, 27b, was studied for mineralization of osteoblast cells and expression of marker genes, viz. BMP-2, RUNX-2 & Osx, involved in osteogenesis. Molecular docking analysis performed for 27b showed its possible interactions with estrogen receptor-α and -β (ER-α and ER-β) as well as the vitamin-D receptor (VDR).
- Ahmad, Mohd. Imran,Raghuvanshi, Dushyant Singh,Singh, Sarita,John, Aijaz A.,Prakash, Ravi,Nainawat, Kripa Shankar,Singh, Divya,Tripathi, Shubhandra,Sharma, Ashok,Gupta, Atul
-
p. 2381 - 2394
(2016/12/18)
-
- Combinatorial synthesis of structurally diverse triazole-bridged flavonoid dimers and trimers
-
Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.
- Sum, Tze Han,Sum, Tze Jing,Galloway, Warren R. J. D.,Collins, Súil,Twigg, David G.,Hollfelder, Florian,Spring, David R.
-
-
- Induction of targeted osteogenesis with 3-aryl-2H-benzopyrans and 3-aryl-3H-benzopyrans: Novel osteogenic agents
-
Development of target oriented chemotherapeutics for treatment of chronic diseases have been considered as an important approach in drug development. Following this approach, in our efforts for exploration of new osteogenic leads, substituted 3-aryl-2H-be
- Gupta, Atul,Ahmad, Imran,Kureel, Jyoti,Hasanain, Mohammad,Pandey, Praveen,Singh, Sarita,John, Aijaz A.,Sarkar, Jayanta,Singh, Divya
-
-
- Novel daidzein analogs and their in vitro anti-influenza activities
-
A series of novel isoflavonoids were synthesized based on structural modifications of daidzein, an active ingredient of traditional Chinese medicine (TCM) and evaluated for their anti-influenza activity, in vitro, against H1N1 Tamiflu-resistant (H1N1 TR) virus in the MDCK cell line. Among them, 4-oxo-4H-1-benzopyran-8-carbaldehydes 11a-11g were most promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent. 3-(4-Bromophenyl)-7-hydroxy-4-oxo-4H-1-benzopyran-8-carboxaldehyde (11c) displayed the best inhibitory activity (EC50, 29.0 μM) and selectivity index (SI>10.3). Analysis of the structure£activity relationships (SAR) indicated that both the non-naturally-occurring Br-substituted B-ring and appropriate CHO and OH groups on the A-ring might be critical for the activity and selectivity against H1N1 TR influenza viruses.
- Chung, Shu-Ting,Huang, Yi-Ting,Hsiung, Hsin-Yi,Huang, Wen-Hsin,Yao, Chen-Wen,Lee, An-Rong
-
p. 685 - 696
(2015/04/27)
-
- Synthesis and anti-tumor activities of novel oxazinyl isoflavonoids
-
The design, synthesis and biological evaluation of a novel series of oxazinyl isoflavonoids is described. Several analogs were shown to exhibit growth inhibitory effects against SKOV-3, DU-145 and HL-60 human colon cancer cell lines with IC50 values in the micromolar range. The cellular potency of compounds 7e and 12h were found to have greater in vitro inhibitory activities than phenoxodiol, the parental compound currently in late-stage clinical trials for the treatment of cancer. The results shown are suitable for further lead optimization.
- Wang, Dun,Hou, Like,Wu, Lirong,Yu, Xin
-
scheme or table
p. 513 - 520
(2012/05/05)
-
- Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: Structure-activity analysis
-
The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79. A large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones as well as their analogs (54 in total) were synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated a possible mechanism of their ICAM-1 inhibitory activities. The most active compound was found to be 79. Copyright
- Kumar, Sarvesh,Reddy L, Chandra Shekhar,Kumar, Yogesh,Kumar, Amit,Singh, Brajendra K.,Kumar, Vineet,Malhotra, Shashwat,Pandey, Mukesh K.,Jain, Rajni,Thimmulappa, Rajesh,Sharma, Sunil K.,Prasad, Ashok K.,Biswal, Shyam,Van Der Eycken, Erik,Depass, Anthony L.,Malhotra, Sanjay V.,Ghosh, Balaram,Parmar, Virinder S.
-
experimental part
p. 368 - 377
(2012/07/31)
-
- Design, synthesis and molecular simulation studies of dihydrostilbene derivatives as potent tyrosinase inhibitors
-
The synthesis, molecular modeling and biological evaluation of substituted deoxybenzoins and optimized dihydrostilbenes are reported. Preliminary structure-activity relationship data were elucidated and lead compounds suitable for further optimization wer
- Vontzalidou, Argyro,Zoidis, Grigoris,Chaita, Eliza,Makropoulou, Maria,Aligiannis, Nektarios,Lambrinidis, George,Mikros, Emmanuel,Skaltsounis, Alexios-Leandros
-
supporting information; experimental part
p. 5523 - 5526
(2012/09/22)
-
- Synthetic analogs of daidzein, having more potent osteoblast stimulating effect
-
A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein.
- Yadav, Dinesh K.,Gautam, Abnish K.,Kureel, Jyoti,Srivastava, Kamini,Sahai, Mahendra,Singh, Divya,Chattopadhyay, Naibedya,Maurya, Rakesh
-
scheme or table
p. 677 - 681
(2011/03/18)
-
- One step synthesis of 2-hydroxymethylisoflavone and their osteogenic activity
-
An efficient one step synthesis of new 2-hydroxymethylisoflavone is reported. A series of deoxybenzoin was subjected to cyclization with glyoxal in the presence of basic condition (KOH/EtOH) to afford the 2-hydroxymethyl isoflavone. The structures of comp
- Kumar, Manmeet,Rawat, Preeti,Kureel, Jyoti,Singh, Anuj Kumar,Singh, Divya,Maurya, Rakesh
-
experimental part
p. 1706 - 1709
(2011/05/11)
-
- PROCESS FOR PREPARING 2,4-DIHYDROXYPHENYL 4-METHOXYBENZYL KETONES
-
The invention relates to a process for preparing 2,4-dihydroxyphenyl 4-methoxybenzyl ketones of the formula (I) by Friedel-Crafts acylation in hydrogen fluoride (HF). 2,4-Dihydroxyphenyl 4-methoxybenzyl ketones of the formula (I) in which R1 an
- -
-
Page/Page column 2
(2010/06/11)
-
- In vivo evaluation of substituted 3-phenyl,7-methoxy-benzopyrans as modified estrogens
-
Substituted 3-phenyl,7-methoxy-benzopyran derivatives and vitamin D 3 (cholecalciferol, 1) were evaluated for their estrogen agonistic and antagonistic activities in immature female Sprague-Dawley rat model. The benzopyran derivatives 17 and 18
- Gupta, Atul,Keshri, Govind,Singh,Ray, Suprabhat
-
scheme or table
p. 25 - 32
(2010/11/18)
-
- Synthesis and structural study on heterocyclic compounds 7-decanoyloxy-3-(4′-substitutedphenyl)-4H-1-benzopyran-4-ones: Crystal structure of 7-decanoyloxy-3-(4′-methylphenyl)-4H-1-benzopyran-4-one
-
Six new isoflavone-based esters, 7-decanoyloxy-3-(4′-substitutedphenyl)-4H-1-benzopyran-4-ones, derived from 1,3-benzenediol (resorcinol) and different para substituted phenylacetic acids have been synthesized and characterized. The molecular structures of the title compounds were elucidated with the employment of physical measurements and spectroscopic techniques (FTIR, 1D and 2D NMR). The conformation of 7-decanoyloxy-3-(4′-methylphenyl)-4H-1-benzopyran-4-one was determined by single crystal X-ray diffraction analysis of which the title compound crystallized into triclinic lattice with P-1 space group. Crystal structure of the title compound also revealed that the two phenyl rings of the central moiety were planar whilst the heterocyclic ring was found to pucker slightly from the mean plane.
- Yeap, Guan-Yeow,Yam, Wan-Sinn,Dominiak, Paulina,Ito, Masato M.
-
experimental part
p. 25 - 33
(2010/06/16)
-
- Synthesis and biological evaluation of isoflavone fatty acid esters with potential weight loss and hypolipidemic activities
-
A series of isoflavone fatty acid esters were designed on the basis of endogenous oleoyl-estrone using estrogen moiety modification strategy. Ten new compounds were synthesized, and their body weight loss and hypolipidemic bioactivities were assayed. Some of these novel compounds could effectively inhibit the differentiation of 3T3-L1 preadipocytes in vitro. The most potent compound 1a significantly decreased the body weight and white adipose tissue weight in a high-fat diet-induced rat model. Also, compound 1a showed good hypolipidemic activity and low toxicity.
- Xiang, Hua,Zhao, Wei,Xiao, Hong,Qian, Lei,Yao, Yao,Li, Xiao-Bo,Liao, Qing-Jiang
-
experimental part
p. 3036 - 3042
(2010/07/06)
-
- Metronidazole-deoxybenzoin derivatives as anti-Helicobacter pylori agents with potent inhibitory activity against HPE-induced interleukin-8
-
A series of new metronidazole-deoxybenzoin derivatives were synthesized and evaluated for their antimicrobial activity against Helicobacter pylori. Highly selective anti-H. pylori activity was also observed in synthesized compounds. Compound 34 exhibited
- Luo, Yin,Li, Huan-Qiu,Zhou, Yang,Li, Zi-Lin,Yan, Tao,Zhu, Hai-Liang
-
experimental part
p. 1110 - 1116
(2011/02/21)
-
- Synthesis and structure-activity relationship study of deoxybenzoins on relaxing effects of porcine coronary artery
-
Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC50 = 3.30 μM (Emax = 100%, n = 7) and 2,4-dihydroxy-4′-methoxydeoxybenzoin EC50 = 3.70 μM (E max = 100%, n = 5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure-activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H ≤ p-OMe > p-OH > o-OMe > m,p-diOMe ≤ m-OMe.
- Lu, Tzy-Ming,Kuo, Daih-Huang,Ko, Horng-Huey,Ng, Lean-Teik
-
experimental part
p. 10027 - 10032
(2011/05/17)
-
- Potential antioxidants and tyrosinase inhibitors from synthetic polyphenolic deoxybenzoins
-
Deoxybenzoins (DOBs) are one-pot synthetic precursors of isoflavones with feature analogous to those beneficial polyphenols such as resveratrol (stilbene) and phloretin (dihydrochalcone). In this study, seventeen polyphenolic DOBs were synthesized and evaluated by various antioxidant assays and tyrosinase inhibitory effect in vitro. Results displayed that these DOBs are powerful antioxidants; for example, 2,3,4-trihydroxy-3′,4′-dimethoxydeoxybenzoin possesses an excellent anti-lipid peroxidation activity (IC50 = 0.72 ± 0.16 μM), whilst 2,4,4′,5-tetrahydroxydeoxybenzoin showed good DPPH radical scavenging activity (IC50 = 0.69 ± 0.04 μM), which were better than Trolox and vitamin C. Besides exhibiting a weak metal chelating effect, these DOBs were effective in scavenging ABTS{radical dot}+ and superoxide anion (O2{radical dot} -) radicals. DOBs also exhibited potent mushroom tyrosinase inhibitory activity; for example 2,3,4′-trihydroxy-4-methoxydeoxybenzoin displayed stable and significant inhibitory effect on tyrosinase activity, with IC50 values 43.37, 43.10 and 46.10 μM at incubation intervals of 0.5, 1.5, and 2.5 h, respectively. These results suggest that, with the advantage of being readily synthesizable small molecules, DOBs can be potentially developed into clinical and industrial antioxidants. Crown Copyright
- Ng, Lean-Teik,Ko, Horng-Huey,Lu, Tzy-Ming
-
experimental part
p. 4360 - 4366
(2009/10/17)
-
- Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
-
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
-
experimental part
p. 346 - 360
(2009/12/27)
-
- 7-Hydroxy-benzopyran-4-one derivatives: A novel pharmacophore of peroxisome proliferator-activated receptor α and -γ (PPARα and γ) dual agonists
-
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.
-
experimental part
p. 6835 - 6850
(2010/04/04)
-
- Simple and efficient synthesis of (±)-equol and related derivatives
-
A simple and efficient synthesis of (±)-equol and related derivatives in good yields from inexpensive starting materials has been described. Georg Thieme Verlag Stuttgart.
- Gupta, Atul,Ray, Suprabhat
-
body text
p. 3783 - 3786
(2009/06/17)
-
- Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease
-
Twenty polyphenols were synthesized and evaluated for their effect on Helicobacter pylori urease. Among these compounds, 4-(p-hydroxyphenethyl)pyrogallol (15) (IC50 = 0.03 mM) and 7,8,4′-trihydroxyisoflavone (19) (IC50 = 0.14 mM) showed potent inhibitory activities, and inhibited Helicobacter pylori urease in a time-dependent manner. The structure-activity relationship of these polyphenols revealed: the two ortho hydroxyl groups were essential for inhibitory activity of polyphenol. When the C-ring of isoflavone was broken, the inhibitory activity markedly decreased. As for deoxybenzoin, the carboxyl group was clearly detrimental.
- Xiao, Zhu-Ping,Shi, Da-Hua,Li, Huan-Qiu,Zhang, Li-Na,Xu, Chen,Zhu, Hai-Liang
-
p. 3703 - 3710
(2008/02/07)
-
- Efficient and simple synthesis of substituted 3-phenyl-7-methoxybenzopyrans as pseudo-vitamin-D3 analogs
-
An efficient and simple synthesis of substituted 3-phenyl-7- methoxybenzopyrans as pseudo-vitamin-D3 analogs in good yields under mild reaction conditions is described. Copyright Taylor & Francis Group, LLC.
- Gupta, Atul,Ray, Suprabhat
-
p. 3119 - 3126
(2008/02/12)
-
- Biocatalytic acylation studies on novel 3-aryl-3-hydroxymethyl-2, 3-dihydro-4H-1-benzopyran-4-ones
-
(±)-3-Aryl-3-hydroxymethy1-2,3-dihydro-4H-1-benzopyran-4-ones have been synthesized in four steps starting with the coupling of resorcinol with corresponding phenylacetic acid leading to the formation of 2,4-dihydroxyphenyl aryl ketones, which upon monome
- Kumar, Vijayendra,Kumar, Rajesh,Raunak,Poonam,Sharma, Sunil K,Prasad, Ashok K,Cholli, Ashok L,Olsen, Carl E,Parmar, Virinder S
-
p. 1501 - 1510
(2008/09/19)
-
- Microwave-promoted synthesis of polyhydroxydeoxybenzoins in ionic liquids
-
A microwave-promoted synthesis of polyhydroxydeoxybenzoins and -phenylpropanones has been developed, using bis{(trifluoromethyl)sulfonyl}amine (HNTf2) or BF3·OEt2 in an ionic liquid solvent.
- Hakala, Ullastiina,W?h?l?, Kristiina
-
p. 8375 - 8378
(2007/10/03)
-
- A convenient one-pot synthesis of 7-hydroxy-isoflavones from resorcinol with substituted phenylacetic acids
-
A mild and highly efficient one-pot synthesis of 7-hydroxy-isoflavones is reported. The acylation of resorcinol with various phenyl acetic acids in molten zinc chloride affords an intermediate deoxybenzoin which without isolation is subjected to cyclization with N,N-dimethylformamide in the presence of boron trifluoride diethyl etherate and methanesulfonyl chloride to afford the 7-hydroxy-isoflavone without the formation of any by-product.
- Singh, Himanshu,Pratap, Ram
-
p. 8161 - 8163
(2007/10/03)
-
- Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design
-
The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional a
- Dymock, Brian W.,Barril, Xavier,Brough, Paul A.,Cansfield, Julie E.,Massey, Andrew,McDonald, Edward,Hubbard, Roderick E.,Surgenor, Allan,Roughley, Stephen D.,Webb, Paul,Workman, Paul,Wright, Lisa,Drysdale, Martin J.
-
p. 4212 - 4215
(2007/10/03)
-
- PREPARATION METHOD OF 2-PHENYLACETOPHENONE DERIVATIVES
-
Disclosed is a preparation method of 2-phenylacetophenone derivatives which are used as key intermediates in total syntheses of coumestans and isoflavonoids such as coumestrol, genistein and daidzein which are phytoestrogens contained in soybean and black
- -
-
Page/Page column 8; 9
(2008/06/13)
-
- ISOXAZOLE COMPOUNDS AS INHIBITORS OF HEAT SHOCK PROTEINS
-
Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): -Ar1-(Alk1)p-(Z)r-(Alk2)S-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1and Alk2 are optionally substituted divalent Cl-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, -S-, -(C=O)-, -(C=S)-, -SO2-, -C(=O)O-, -C(=O)NRA-, -C(=S)NRA-, - SO2NRA-, -NRAC(=O)-, -NRASO2- or -NRA- wherein RA is hydrogen or Cl-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and R3 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.
- -
-
-
- A convenient one-pot synthesis of 2-(alkylthio)isoflavones from deoxybenzoins using a phase transfer catalyst
-
A convenient phase transfer catalysis procedure for the synthesis of 2-(alkylthio)isoflavones is described. A number of compounds of potential pharmaceutical interest can be prepared in a single step at ambient conditions from various, easily accessible d
- Kim, Young-Woo,Brueggemeier, Robert W
-
p. 6113 - 6115
(2007/10/03)
-
- An efficient 'one pot'synthesis of isoflavones
-
Initial formation of deoxybenzoin 3 from phenyl acetic acid 1 and phenol 2 in the presence of BF3.Et2O followed by its treatment at room temperature with N, N'-dimethyl (chloromethylene) ammonium chloride, generated by reacting PCl5 with DMF provides a mild and efficient route for a 'one pot' synthesis of Isoflavones in high yields.
- Balasubramanian, Sreenivasan,Nair, Muraleedharan G.
-
p. 469 - 484
(2007/10/03)
-
- The first isolation and crystal structure of a boron difluoro complex (isoflavone yellow). Biologically active intermediates produced during isoflavone synthesis
-
The yellow intermediate 4f produced during the reaction of the deoxybenzoin 3f with N,N'-dimethyl(chloromethylene)ammonium chloride in the presence of BF3*Et2O prior to the formation of the corresponding isoflavone was isolated for the first time and characterized by NMR, MS and single-crystal X-ray diffraction techniques. These yellow intermediates showed anticancer, nematicidal and mosquitocidal activities.
- Balasubramanian, Sreenivasan,Ward, Donald L.,Nair, Muraleedharan G.
-
p. 567 - 570
(2007/10/03)
-
- Syntheses of novel hapten-protein conjugates for production of highly specific antibodies to formononetin, daidzein and genistein
-
The syntheses of novel hapten-carrier protein conjugates are described. Isoflavones functionalised in C2 were coupled to bovine serum albumin or swine thyroglobulin. The antibodies obtained were used for the development of ELISAs (enzyme-linked immunosorb
- Le Houérou, Cyril,Bennetau-Pelissero, Catherine,Lamothe, Valérie,Le Menn, Fran?oise,Babin, Pierre,Bennetau, Bernard
-
p. 295 - 301
(2007/10/03)
-
- Process for the preparation of isoflavones
-
A process for the preparation of an isoflavone from a 2'-hydroxydeoxybenzoin(I) is described. The process uses prepared N,N'-dimethyl(chloromethylene) ammonium chloride as a reactant with (I) in borontrifluoride etherate or other Lewis acid as a solvent. The isoflavones are known biologically active compounds.
- -
-
-
- Microwave-Mediated Synthesis of Anticarcinogenic Isoflavones from Soybeans
-
Soybean isoflavonoids, 7,4'-dihydroxyisoflavone (daidzein), 7-hydroxy-4'-methoxyisoflavone (formononetin), 5,7,4'-trihydroxyisoflavone (genistein), and 5,7-dihydroxy-4'-methoxyisoflavone (biochanin A), were synthesized in high yields by cyclization of their corresponding ketones in a conventional microwave oven. Keywords: Microwave synthesis; isoflavones; daidzein; genistein; formononetin; biochanin A
- Chang, Yu-Chen,Nair, Muraleedharan G.,Santell, Ross C.,Helferich, William G.
-
p. 1869 - 1871
(2007/10/02)
-
- Biosynthesis of the A/B/C/D-Ring System of the Rotenoid Amorphigenin by Amorpha fruticosa Seedlings
-
With phenylalanine as the starting point, the biosynthesis of the characteristic rotenoid A/B/C/D-ring system of amorphigenin is studied using Amorpha fruticosa seedlings.The course of the biosynthesis can be divided into four phases represented by the bordered and interconnecting Schemes 1, 3, 6 and 7 which summarise the Chalcone-Flavanone Phase, the Flavanone-Isoflavone Phase, the Hydroxylation/Methoxylation Phase and the Rotenoid Phase.By using an INADEQUATE NMR experiment involving the administration of acetate, the type of folding forming ring-D isdemonstrated by 13C-13C coupling and is interpreted as involving a polyketide containing a glutaconate segment which cyclises by a Claisen condensation.The resulting chalcone is cyclised, enzymically and stereospecifically, to 4',7-dihydroxyflavanone.The latter flavanone undergoes aryl migration, in a manner similar to that found in isoflavone biosynthesis, to give 7-hydroxy-4'-methoxyisoflavone.Possible mechanisms for the flavanone-isoflavone rearrangement are discussed, including a proposal that the initiating step involves attack on ring-A and is similar to the first stage of the aromatic hydroxylation of tyrosine to dopa.Although possessing no 4'-hydroxy group in ring-A, the mechanism is also applicable to the recently discovered rotenoids of the Boerhaavia and Iris type, and it provides an explanation for the biogenesis of natural spirobenzocyclobutanes from dihydroeucominoids.Six suitably substituted isoflavonoids labelled with 13C or 3H are synthesized and are used to show that the next hydroxylation (and probably methylation) involves C-3' rather than C-2' in 7-hydroxy-4'-methoxyisoflavone.Whilst the methylations involveS-adenosylmethionine, the hydroxylating enzymes are probably very similar to the flavanone-isoflavone-rearranging enzyme.The closure of ring-B to form finally the rotenoid system probably involves conjugate addition of a methoxyl radical.Prenylation and oxidative modifications are characteristically late-stage processes.
- Bhandari, Prabha,Crombie, Leslie,Daniels, Peter,Holden, Ian,Bruggen, Nicholas Van,Whiting, Donald A.
-
p. 839 - 850
(2007/10/02)
-
- Expedient Synthesis of Polyhydroxyisoflavones
-
A general and direct synthesis of polyhydroxy isoflavones (3-phenyl-4H-1-benzopyran-4-ones) starting from the corresponding unprotected phenols and arylacetic acids is described.The aryl rings may carry additional alkyl, methoxy and/or halogeno groups.Intermediate polyhydroxydeoxybenzoins (1,2-diphenylethanones) can also be isolated in good yields.
- Waehaelae, Kristiina,Hase, Tapio A.
-
p. 3005 - 3008
(2007/10/02)
-