- Structural modification and antihypertensive activity study of formononetin derivatives
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A series of formononetin derivatives with substituted benzyloxy groups on the 4′ position of isoflavone were designed and synthesized. Their vasodilative activities were evaluated by wire myograph system on isolated rat mesenteric arterial ring. The preli
- Guo, Qiu-Hong,Li, Jing,Ma, Dong-Lai,Zhou, Li,Zuo, Sai-Jie
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- Synthesis of structurally diverse biflavonoids
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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.
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supporting information
p. 5089 - 5101
(2018/05/23)
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- Combinatorial synthesis of structurally diverse triazole-bridged flavonoid dimers and trimers
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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.
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- Design and synthesis of 3-arylbenzopyran based non-steroidal vitamin-D3 mimics as osteogenic agents
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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
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p. 2381 - 2394
(2016/12/18)
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- Induction of targeted osteogenesis with 3-aryl-2H-benzopyrans and 3-aryl-3H-benzopyrans: Novel osteogenic agents
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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
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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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supporting information
p. 881 - 884
(2015/02/19)
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- Free-radical-scavenging, antityrosinase, and cellular melanogenesis inhibitory activities of synthetic isoflavones
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In this study, we examined the potential of synthetic isoflavones for application in cosmeceuticals. Twenty-five isoflavones were synthesized and their capacities of free-radical-scavenging and mushroom tyrosinase inhibition, as well as their impact on cell viability of B16F10 murine melanoma cells and HaCaT human keratinocytes were evaluated. Isoflavones that showed significant mushroom tyrosinase inhibitory activities were further studied on reduction of cellular melanin formation and antityrosinase activities in B16F10 melanocytes in vitro. Among the isoflavones tested, 6-hydroxydaidzein (2) was the strongest scavenger of both ABTS.+ and DPPH. radicals with SC50 values of 11.3±0.3 and 9.4±0.1 μM, respectively. Texasin (20) exhibited the most potent inhibition of mushroom tyrosinase (IC50 14.9±4.5 μM), whereas retusin (17) showed the most efficient inhibition both of cellular melanin formation and antityrosinase activity in B16F10 melanocytes, respectively. In summary, both retusin (17) and texasin (20) exhibited potent free-radical-scavenging capacities as well as efficient inhibition of cellular melanogenesis, suggesting that they are valuable hit compounds with potential for advanced cosmeceutical development.
- Lu, Tzy-Ming,Ko, Horng-Huey,Ng, Lean-Teik,Hsieh, Yen-Pin
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p. 963 - 979
(2015/06/25)
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- Design and synthesis of ERα/ERβ selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents
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Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERα and ERβ selective activity. Coumarin prototype compounds 18 & 19 were found to be ERα selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER -ve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE-ERα dependent transactivation and induce ERβ activity. This specific upregulation of ERβ isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERα and ERβ revealed that most of the compounds showed ERα and ERβ-mediated action, except compound 28, which showed selectivity to ERα only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERα and ERβ active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERβ binding cavity may be responsible for its potential biological response. The Royal Society of Chemistry.
- Hussain, M. Kamil,Ansari, M. Imran,Yadav,Gupta, Puneet K.,Gupta,Saxena,Fatima,Manohar,Kushwaha,Khedgikar,Gautam,Kant, Ruchir,Maulik,Trivedi,Dwivedi,Kumar, K. Ravi,Saxena,Hajela
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p. 8828 - 8845
(2014/03/21)
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- Synthetic analogs of daidzein, having more potent osteoblast stimulating effect
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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
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scheme or table
p. 677 - 681
(2011/03/18)
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- One step synthesis of 2-hydroxymethylisoflavone and their osteogenic activity
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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
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experimental part
p. 1706 - 1709
(2011/05/11)
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- Synthesis and biological evaluation of isoflavone fatty acid esters with potential weight loss and hypolipidemic activities
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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
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experimental part
p. 3036 - 3042
(2010/07/06)
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- ANTIESTROGENS FOR BREAST CANCER THERAPY
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This invention provides a compound having the structure wherein α, q, X, and R1-R14 are defined herein, or a salt thereof. This invention also provides a process for preparing the above compound, a pharmaceutical composition comprisi
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Page/Page column 88-89
(2010/10/03)
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- Simple and efficient synthesis of (±)-equol and related derivatives
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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
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experimental part
p. 3783 - 3786
(2009/06/17)
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- BENZOPYRANONE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Benzopyranone Compounds having the following structure: (I) wherein R1, R2, X, Y and n are as defined herein, are disclosed. The Benzopyranone Compounds are useful for treating or preventing a bone-resorbing disease, a neoplastic dis
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Page/Page column 42-43; 48-49
(2010/02/11)
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- Benzopyranone compounds, compositions thereof, and methods of treatment therewith
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Benzopyranone compounds having the following structure: wherein R1, X, Y and n are as defined here, are disclosed. The compounds of formula (I), wherein R1 is H, can be prepared by demethylation of the corresponding phenolic methyl e
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- Lead identification of a potent benzopyranone selective estrogen receptor modulator
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Starting from a phenol screening hit (6), three series of benzopyranone selective estrogen receptor modulators (SERMs) have been designed, synthesized, and analyzed for both estrogen receptor alpha binding affinity and in vitro activity in two cell assays. The lead compound identified, SP500263 (13), was more potent than raloxifene and tamoxifen in a cell-based assay measuring inhibition of interleukin-6 release.
- McKie, Jeffrey A.,Bhagwat, Shripad S.,Brady, Helen,Doubleday, Mary,Gayo, Leah,Hickman, Mathew,Jalluri, Ravi K.,Khammungkhune, Sak,Kois, Adam,Mortensen, Deborah,Richard, Normand,Sapienza, John,Shevlin, Graziella,Stein, Bernd,Sutherland, May
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p. 3407 - 3410
(2007/10/03)
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- Benzopyrazone compounds, compositions thereof, and methods of treatment therewith
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Benzopyranone compounds having the following structure: wherein R1, X, Y and n are as defined here, are disclosed. The compounds of formula (I), wherein R1is H, can be prepared by demethylation of the corresponding phenolic methyl et
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- An efficient 'one pot'synthesis of isoflavones
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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.
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p. 469 - 484
(2007/10/03)
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- The first isolation and crystal structure of a boron difluoro complex (isoflavone yellow). Biologically active intermediates produced during isoflavone synthesis
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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.
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p. 567 - 570
(2007/10/03)
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- Synthesis of 3-aryl-1-(4-methoxyphenyl)-2--2-propen-1-ones and benzopyran derivatives
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Acylation of anisole (5) or m-methoxyphenol (6) with arylacetic acid (7 or 8) gives the corresponding deoxybenzoins (9-12) along with minor isomeric product 13 in one case.Acetylation of 4-hydroxy-4'-methoxydeoxybenzoin (10) with acetic anhydride in pyridine or its alkylation with N-(2-chloroethyl)diethylammonium/pyrrolidinium chloride furnishes the corresponding deoxybenzoin derivatives (14-16).Condensation of 9, 11, 15 and 16 with araldehydes affords the corresponding title compounds 2-propen-1-ones (17, 19 and 21-23). 1-(2-Hydroxy-4-methoxyphenyl)-2,3-diphenyl-2-propen-1-one (19) is isomerized using silica gel or hydrochloric acid to 2,3-trans-2,3-dihydro-7-methoxy-2,3-diphenyl-4H-1-benzopyran-4-one (24) which on sodium borohydride reduction provides a mixture of isomeric benzopyranols (25).Dehydration of 25 gives 7-methoxy-2,3-diphenyl-2H/4H-1-benzopyran (27).The isomeric 7-methoxy-2,4-diphenyl-2H/4H-1-benzopyran (28) is prepared by the reaction of 2,3-dihydro-7-methoxy-2-phenyl-4H-1-benzopyran-4-one (26) with phenylmagnesium bromide.Condensation of 11 with 7 in acetic anhydride/triethylamine furnishes 4-benzyl-7-methoxy-3-phenyl-2H-1-benzopyran-2-one (29).
- Verma, Braham S.,Dhindsa, Kuldip Singh,Sangwan, Naresh K.
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p. 239 - 243
(2007/10/02)
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