- The synthetic preparation of naturally-occurring aromatase inhibitors, morachalcone A, isogemichalcone B, and isogemichalcone C
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A convergent synthesis applicable to the preparation of oxidized prenylchalcones is reported that relies on key Claisen-Schmidt, Mitsunobu, and vinyl/benzyl Stille coupling operations. The synthetic strategy was applied towards the preparation of the natu
- Brandt, Drew R.,Pannone, Kristina M.,Romano, Joseph J.,Casillas, Eduard G.
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Read Online
- First total synthesis of (±)-sepicanin A
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A facile approach for the first total synthesis of naturally occurring geranylated flavanoids sepicanin A has been obtained with total yield 16% starting from 2,4,6-trihydroxyacetophenone after four steps. The key step was the protic acids (HCl or p-TsOH)
- Yang, Jin Hui,Huang, Wen Qian,Luo, Jun Shan,Guo, Dong Dong,Zhang, Yu Heng,Li, Hong Jun
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- Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers
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Four ring-closed analogs of natural prenylated chalcone desmethylxanthohumol (1) and their dimers were synthesized from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one in five and six linear steps, respectively. The structures of the eigh
- Teng, Yuou,Li, Xuzhe,Yang, Ke,Li, Xuehui,Zhang, Zijun,Wang, Luyao,Deng, Zhijie,Song, Binbin,Yan, Zhihong,Zhang, Yongmin,Lu, Kui,Yu, Peng
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Read Online
- COMBINATION TREATMENT OF BACTERIAL INFECTION
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The present invention resides in the discovery that combined use of kuraridin (or any one of its analogs) and epicatechin gallate (ECG) can provide heightened level of antimicrobial activity, especially for the suppression of bacteria of the Staphylococcus aureus and Staphylococcal species. Compositions, kits, and methods for the combination use are disclosed.
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Paragraph 0141; 0142
(2020/06/08)
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- Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship
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To explore the structure-activity relationships on the inhibitory activity of flavanonols against nitric oxide (NO) production in inflammatory cells, we synthesized 19 flavanonols which shared a common 3,5,7-trihydroxychroman scaffold. A range of substitutions was included in the B ring in order to investigate the structure-activity relationship. We also succeeded in isolating stereoisomers from 16 of the flavanonols using chiral column chromatography. The inhibitory effects of these compounds on NO production were examined in RAW 264.7 cells (a murine macrophage-like cell line), which were activated by lipopolysaccharide (LPS). We only observed inhibitory activity against NO production in (2R,3R) stereoisomers, while the inhibitory activities of (2S,3S) stereoisomers were significantly weaker. We also evaluated the free radical scavenging potential of the flavanonols using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Each stereoisomer indicated the equivalent DPPH scavenging potential as expected. The radical scavenging activity was not correlated with the inhibitory activity against NO. The inhibition of NO production by flavanonols is stereospecific and cannot simply be explained by their radical scavenging activity. We propose the possible existence of a 'target' molecule for flavanonols which is involved in the production and/or regulation of NO in RAW 264.7 cells.
- Jiang, Wen-Jun,Ishiuchi, Kan'Ichiro,Furukawa, Megumi,Takamiya, Tomoko,Kitanaka, Susumu,Iijima, Hiroshi
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p. 6922 - 6929
(2015/11/11)
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- Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: A new target for a privileged structure
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The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α77 nicotinic function. The most potent compound (2,4,2-2,5-2-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.
- Balsera, Beatriz,Mulet, José,Fernández-Carvajal, Asia,Torre-Martínez, Roberto De La,Ferrer-Montiel, Antonio,Hernández-Jiménez, José G.,Estévez-Herrera, Judith,Borges, Ricardo,Freitas, Andiara E.,López, Manuela G.,García-López, M. Teresa,González-Mu?iz, Rosario,Pérez De Vega, María Jesús,Valor, Luis M.,Svobodová, Lucie,Sala, Salvador,Sala, Francisco,Criado, Manuel
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p. 724 - 739
(2015/02/19)
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- Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors
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In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active
- Baek, Kyung Hye,Karki, Radha,Lee, Eung-Seok,Na, Younghwa,Kwon, Youngjoo
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- SMALL MOLECULE INHIBITORS OF IL-6 AND USES THEREOF
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In one aspect, the invention relates to substituted 2-(lH-indol-3-yl)ethanol analogs and substituted 3,3a,8,8a-tetrahydro-2H-furo[2,3-b]indole analogs, derivatives thereof, and related compounds, which are useful as inhibitors of IL-6 mediated activation of the Jak2/STAT3 pathway; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a IL6 dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00900; 00933
(2013/03/26)
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- Multidimensional optimization of promising antitumor xanthone derivatives
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A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.
- Azevedo, Carlos M.G.,Afonso, Carlos M.M.,Sousa, Diana,Lima, Raquel T.,Helena Vasconcelos,Pedro, Madalena,Barbosa, Jo?o,Corrêa, Arlene G.,Reis, Salette,Pinto, Madalena M.M.
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p. 2941 - 2959
(2013/07/05)
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- HETEROAROMATIC-CONTAINING COMPOUND, OPTICAL MATERIAL AND OPTICAL ELEMENT
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There are provided a heteroaromatic-containing compound represented by the following general formula (1), and an optical material including the heteroaromatic-containing compound. Formula 1 General Formula (1) wherein R1 and R2 are each independently a hydrogen atom or a methyl group, Ar1 is an aryl group which may have a substituent, and A is an aromatic hydrocarbon group. The R1 and R2 can be a hydrogen atom, and Ar1 can be a phenyl group.
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(2011/07/30)
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- A Wacker-Cook synthesis of isoflavones: formononetine
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A total synthesis of the isoflavone formononetine 1 by an oxidative Pd-mediated cyclization of α-methylenedeoxybenzoins 4a-c is described. Substrates 4a-c were rapidly assembled using 'protected cyanohydrin' chemistry.
- Granados-Covarrubias, Evin H.,Maldonado, Luis A.
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body text
p. 1542 - 1545
(2009/06/18)
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- The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity
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(Chemical Equation Presented) Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at ~700 μM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
- Donnelly, Alison C.,Mays, Jared R.,Burlison, Joseph A.,Nelson, John T.,Vielhauer, George,Holzbeierlein, Jeffrey,Blagg, Brian S. J.
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p. 8901 - 8920
(2009/04/11)
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- Synthesis of luminacin D
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The total synthesis of luminacin D (1) is reported on the basis of two aldol reactions to form the carbohydrate sector, aldehyde 30. Reaction of aldehyde 30 with the aryllithium intermediate derived from aryl iodide 38, cleavage of the silyl ether, and ox
- Jogireddy, Rajamalleswaramma,Maier, Martin E.
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p. 6999 - 7006
(2007/10/03)
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- Synthesis and PPAR-γ ligand-binding activity of the new series of 2′-hydroxychalcone and thiazolidinedione derivatives
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Fifteen chalcones and three thiazolidinedione (TZD) chalcones were prepared to evaluate their peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand-binding activities. Among the three TZDs, one compound possessed PPAR-γ transactivation potential, while the others showed antagonistic activity against PPAR-γ transactivation. Among the chalcones, compound 5 was the most potent, and structure-activity relationship studies indicated that a methoxyl group in position C-4 and hydroxyl group in position C-4′ or 5′ in chalcone plays a key role in determining the potency of PPAR-γ activation.
- Sang, Hoon Jung,Soo, Young Park,Kim-Pak, Youngmi,Hong, Kyu Lee,Kyong, Soo Park,Kuk, Hyun Shin,Ohuchi, Kazuo,Shin, Hyun-Kyung,Sam, Rok Keum,Soon, Sung Lim
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p. 368 - 371
(2007/10/03)
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- A short synthesis of morachalcone A
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Advanced C-prenylated intermediates for three aromatase inhibitors, including morachalcone A, can be synthesized through a Claisen-Schmidt condensation followed by Florisil-catalyzed [1,3]-sigmatropic rearrangement of a prenyl phenyl ether.
- Romano, Joseph J.,Casillas, Eduard
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p. 2323 - 2326
(2007/10/03)
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- Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues
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Aldose reductase, the key enzyme of the polyol pathway, and oxidative stress are known to play important roles in the complications of diabetes. A drug with potent inhibition of aldose reductase and oxidative stress, therefore, would be a most promising drug for the prevention of diabetic complications. The purpose of this study was to develop new compounds with these dual-effects through synthesis of chalcone derivatives and by examining the structure-activity relationships on the inhibition of rat lens aldose reductase as well as on antioxidant effects. A series of 35 flavonoid derivatives were synthesized by Winget's condensation, oxidation, and reduction of appropriate acetophenones with appropriate benzaldehydes. The inhibitory activity of these derivatives on rat lens aldose reductase and their antioxidant effects, measured using Cu2+ chelation and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in-vitro, were evaluated. Their effect on sorbitol accumulation in the red blood cells, lenses and sciatic nerves of streptozotocin-induced diabetic rats was also estimated. Among the new flavonoid derivatives synthesized, those with the 2′,4′-dihydroxyl groups in the A ring such as 2,4,2′,4′-tetrahydroxychalcone (22), 2,2′,4′-trihydroxychalcone (11), 2′,4′-dihydroxy-2,4-dimethylchalcone (21) and 3,4,2′,4′-tetrahydroxychalcone (18) were found to possess the highest rat lens aldose reductase inhibitory activity in-vitro, their IC50 values (concentration of inhibitors giving 50 % inhibition of enzyme activity) being 1.6 × 10-7, 3.8 × 10-7, 4.0 × 10-7 and 4.6 × 10-7 M, respectively. All of the chalcones tested except 3, 18, 23 with o-dihydroxy or hydroquinone moiety showed a weak free radical scavenging activity. In the in-vivo experiments, however, compound 18 with o-dihydroxy moiety in the B ring showed the strongest inhibitory activity in the accumulation of sorbitol in the tissues. It also showed the strongest activity in transition metal chelation and free radical scavenging activity. Of the 35 4,2′-dihydroxyl and 2′,4′-dihydroxyl derivatives of flavonoid synthesized, including chalcone, flavone, flavanone, flavonol and dihydrochalcone, some chalcone derivatives synthesized were found to possess aldose reductase inhibition and antioxidant activities in-vitro as well as inhibition in the accumulation of sorbitol in the tissues in-vivo. 3,4,2′,4′-Tetrahydroxychalcone (18, butein) was the most promising compound for the prevention or treatment of diabetic complications.
- Lim, Soon Sung,Jung, Sang Hoon,Ji, Jun,Shin, Kuk Hyun,Keum, Sam Rok
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p. 653 - 668
(2007/10/03)
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- The first total synthesis and establishment of absolute structure of luminacins C1 and C2
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Luminacins C1 and C2 (1 and 2), novel angiogenesis inhibitors, have been synthesized from a carbohydrate. The correlation of 1 and 2 confirms their structures to be different only at C1″ and establishes the relative and absolute conf
- Tatsuta, Kuniaki,Nakano, Satoshi,Narazaki, Fumie,Nakamura, Yusuke
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p. 7625 - 7628
(2007/10/03)
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- Total synthesis of (R,S)-sophoraflavanone C
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Sophoratlavanone C, a C-8 geranylflavanone natural product originally isolated from Echinosophora koreensis, has been synthesized in racemic form in six steps, starting from 2,4,6-trihydroxyacetophenone and 2,4- dihydroxybenzaldehyde.
- Huang, Chusheng,Zhang, Zhe,Li, Yulin
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p. 1283 - 1285
(2007/10/03)
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- Synthesis and biological activity of arthrographol and related compounds
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(±)- Arthrographol (1a) and related compounds were synthesized and their inhibitory activities against 5-lipoxygenase were investigated. The l'(Z)-isomer (1b) of arthrographol was found to be three times active than arthrographol itself.
- Miyake, Muneharu,Hanaoka, Yoshiaki,Fujimoto, Yasuo,Sato, Yoshio,Taketomo, Naoki,Yokota, Itsuro,Yoshiyama, Yoshihiro
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p. 665 - 674
(2007/10/03)
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- Synthesis of (+/-)-Arthrographol (Asperfuran)
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Arthrographol, antifungal dihydrobenzofuran, have been synthesized starting from 2,4-dihydroxybenzaldehyde in 10 steps.
- Miyake, Muneharu,Fujimoto, Yasuo
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p. 1683 - 1686
(2007/10/02)
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