- A chalcone derivative, 1m-6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation-induced endothelial dysfunction
-
Background and Purpose: Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential. Experimental Approach: Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by 3H labelling of cholesterol. LDL receptor knockout (Ldlr?/?) mice fed a high-fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation. Key Results: Using ATP-binding cassette transporter A1 (ABCA1) expression we identified the chalcone derivative, 1m-6, which enhances ABCA1 expression and promotes cholesterol efflux in THP-1 macrophages. Moreover, 1m-6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1-regulating miRNAs through nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1) signalling. Additionally, 1m-6 significantly inhibits TNF-α-induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO-1 signalling in HUVECs. In atherosclerosis-prone mice, 1m-6 significantly reduces lipid accumulation and atherosclerotic plaque formation. Conclusion and Implications: Our study demonstrates that 1m-6 produces promising atheroprotective effects by enhancing cholesterol efflux and suppressing inflammation-induced endothelial dysfunction, which opens a new avenue for treating ASCVD. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.
- Chen, Liv Weichien,Tsai, Min-Chien,Chern, Ching-Yuh,Tsao, Tien-Ping,Lin, Feng-Yen,Chen, Sy-Jou,Tsui, Pi-Fen,Liu, Yao-Wen,Lu, Hsien-Jui,Wu, Wan-Lin,Lin, Wei-Shiang,Tsai, Chien-Sung,Lin, Chin-Sheng
-
-
Read Online
- Diastereoselective synthesis of (±)-heliotropamide by a one-pot, four-component reaction
-
The first synthesis of heliotropamide is reported. The preparation of this 2-oxopyrrolidine (γ-lactam) natural product relied on a diastereoselective one-pot, four-component reaction (4CR) for the assembly of the core structure. On the basis of chemical shift correlation and NOESY experiments, the previously unknown alkene geometry of heliotropamide is assigned as E.
- Younai, Ashkaan,Chin, Gregory F.,Shaw, Jared T.
-
-
Read Online
- Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
-
Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88-89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. This journal is
- Lakó, ágnes,Mendon?a, Ricardo,Molnár, Zsófia,Poppe, László
-
p. 40894 - 40903
(2020/11/23)
-
- Ferrocenyl chalcones with O-alkylated vanillins: synthesis, spectral characterization, microbiological evaluation, and single-crystal X-ray analysis
-
O-alkylated vanillin derivatives 2a–f and acetylferrocene react under Claisen–Schmidt conditions, resulting in good-to-high yields of the corresponding ferrocene chalcones 3a–f. None of the resultant compounds 3b–f has been previously described in the literature. All synthesized compounds were characterized by spectral and physical data, whereas two of them, 1-ferrocenyl-3-(4-ethoxy-3-methoxyphenyl)-prop-2-en-1-one (3b) and 1-ferrocenyl-3-(4-buthoxy-3-methoxy-phenyl)-prop-2-en-1-one (3e), were crystalline substances, suitable for single-crystal X-ray analysis, which confirmed undoubtedly their structures. Chalcones 3a–f were tested for their biological activity and demonstrated relatively good in vitro antimicrobial activity towards different strains of bacteria and fungi. The best antibacterial activity is expressed by compounds 3b and 3c, while compound 3d shows the best antifungal activity.
- Mu?kinja, Jovana,Burmud?ija, Adrijana,Ratkovi?, Zoran,Rankovi?, Branislav,Kosani?, Marijana,Bogdanovi?, Goran A.,Novakovi?, Sla?ana B.
-
p. 1744 - 1753
(2016/10/03)
-
- Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents
-
Enlightened by the modification route from Camptothecin (CPT) to Topotecan and based on classical drug design theory, a series of Mannich derivatives of lamellarin D were designed and synthesized in 26-27 steps starting from vanillin and isovanilin. All synthesized compounds were then biologically evaluated for their in vitro anti-cancer activities and Topo I inhibitory activities. The results showed that most target compounds exhibited Topo I inhibitory activities in equivalent level with that of lamellarin D. Compound SL-9 exhibited better Topo I inhibitory activity than that of lamellarin D. Compounds SL-2, SL-3, SL-4, SL-5 and SL-11 exhibited better anti-proliferative activity against HT-29 cells than that of lamellarin D.
- Shen, Li,Xie, Nan,Yang, Bo,Hu, Yongzhou,Zhang, Yongmin
-
p. 807 - 817
(2014/10/15)
-
- IMIDAZOLE COMPOUNDS AS MODULATORS OF FSHR AND USES THEREOF
-
The present invention relates to imidazole compounds, and pharmaceutically acceptable compositions thereof, useful as positive allosteric modulators of follicle stimulating hormone receptor (FSHR).
- -
-
Paragraph 00177
(2015/01/16)
-
- Concurrent synthesis of vanillin and isovanillin
-
A method for concurrent synthesis of vanillin and isovanillin has been developed by a nonregioselective Vilsmeier-Haack reaction of O-alkyl guaiacols. O-Alkylation of guaiacol provided the corresponding O-alkyl guaiacol (1), which was then formylated with N-methylformanilide/phosphorus oxychloride to give a mixture of 4-alkoxy-3-methoxy-benzaldehyde (2) and 3-alkoxy-4- methoxybenzaldehyde (3). Finally, the obtained mixture underwent a selective dealkylation by anhydrous aluminium trichloride, while leaving methyl groups intact to simultaneously achieve the significant fine chemicals vanillin and isovanillin.
- Huang, Wei-Bin,Du, Cai-Yan,Jiang, Jian-An,Ji, Ya-Fei
-
p. 2849 - 2856
(2013/07/26)
-
- Design, synthesis, and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists
-
The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2- methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.
- Crestey, Fran?ois,Jensen, Anders A.,Borch, Morten,Andreasen, Jesper Tobias,Andersen, Jacob,Balle, Thomas,Kristensen, Jesper Langgaard
-
supporting information
p. 9673 - 9682
(2014/01/06)
-
- An efficient synthesis of a potent anti-inflammatory agent, viscolin, and its inducible nitric oxide synthase inhibitory activity
-
A new and efficient synthetic pathway employed the aldol condensation between the acetophenone (3) and vanillin derivative (4) resulted in the precursor chalcone intermediate (14). The target compound viscolin (1) could be afforded through the hydrogenation of the chalcone and followed by deprotection. The present strategy described the development of a more efficient procedure that allowed large-scale production of viscolin for the further research of biological activity both in vitro and in vivo.
- Kuo, Ping-Chung,Chen, Yi-Hsien,Leu, Yann-Lii,Huang, Chieh-Hung,Liao, Yu-Ren,Lee, E.-Jian,Yang, Mei-Lin,Wu, Tian-Shung
-
experimental part
p. 557 - 561
(2012/06/01)
-
- Total synthesis of lamellarins D, H, and R and ningalin B
-
A concise total synthesis of lamellarins D (7 steps), H (7 steps), and R (5 steps) and ningalin B (5 steps) is achieved starting from the corresponding aldehydes and amines. The synthesis features three oxidative reactions as key steps in a biomimetic manner, involving an AgOAc-mediated oxidative coupling reaction to construct the pyrrole core, a Pb(OAc)4-induced oxidative cyclization to form the lactone, and Kita's oxidation reaction to form the pyrrole-arene C-C bond.
- Li, Qingjiang,Jiang, Jingqian,Fan, Aili,Cui, Yuxin,Jia, Yanxing
-
supporting information; experimental part
p. 312 - 315
(2011/03/23)
-
- Synthesis and topoisomerase i inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D
-
A novel 5-oxa-6a,8-diazaindeno[2,1-b]phenanthren-7-one scaffold was designed and synthesized as an active analogue of the cytotoxic marine alkaloid Lamellarin D. The design was based on molecular modeling of the site of interaction of Lamellarin D with DNA-topoisomerase I cleavable complex, whereas the synthesis capitalized on a simple Friedel-Crafts cyclization of indole to a β-carbolinone nucleus. The product exhibited topoisomerase I poisoning activity and submicromolar cytotoxicity on human non-small cell lung cancer H460 cell line.
- Cananzi, Salvatore,Merlini, Lucio,Artali, Roberto,Beretta, Giovanni Luca,Zaffaroni, Nadia,Dallavalle, Sabrina
-
experimental part
p. 4971 - 4984
(2011/10/05)
-
- (DIHYDRO) IMIDAZOISO (5, 1-A) QUINOLINES AS FSH RECEPTOR AGONISTS FOR THE TREATMENT OF FERTILITY DISORDERS
-
The invention relates to imidazoiso[5,1-a]quinoline and 5,6-dihydro-imidazoiso[5,1-a]quinoline derivatives according to general Formula (1) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 48-49
(2010/12/26)
-
- (DIHYDRO)IMIDAZOISO[5,1-A]QUINOLINES
-
The invention relates to imidazoiso[5,1-a]quinoline and 5,6-dihydro-imidazoiso[5,1-a]quinoline derivatives according to general Formula I or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 22; 23
(2010/12/31)
-
- (DIHYDRO)PYRROLO[2,1-A]ISOQUINOLINES
-
The invention relates to 5,6 - dihydropyrrolo [2,1-a] isoquinoline and pyrrolo[2,1-a] isoquinoline derivatives according to general formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 33-34
(2009/10/09)
-
- HYDRAZIDE DERIVATIVES
-
A compound represented by the following general formula (1) or a salt thereof or a hydrate of the foregoing is safe while exhibiting suitable physicochemical stability, and is useful as therapeutic or prophylactic agents for diseases associated with thrombus formation. wherein R1a, R1b, R1c and R1d each independently represent hydrogen, etc., R2 represents optionally substituted phenyl, etc., R3 represents optionally substituted C6-10 aryl, etc., Z1, Z2 and Z3 each independently represent hydrogen, etc., Z4 represents hydrogen, etc. and X represents a single bond or -CO-, etc.
- -
-
Page/Page column 36
(2010/11/28)
-
- Synthesis of both enantiomers of protoberberines via laterally lithiated (S)-4-isopropyl-2-(o-tolyl)-oxazolines
-
The addition of the laterally lithiated (S)-4-isopropyl-2-(o- tolyl)oxazoline (1) to 6,7-dimethoxy-3,4-dihydroisoquinoline (2) proceeded in modest diastereoselectivity. However, the addition products (3a) and (3b) were easily separated by column chromatography over silica gel. Acid-catalyzed lactamization of 3a and 3b followed by LiAlH4-reduction afforded the corresponding optically pure protoberberines (8a) and (8b), respectively. This procedure was successfully applied to the synthesis of both enantiomers of xylopinine and bharatamine.
- Fukuda, Tsutomu,Iwao, Masatomo
-
p. 701 - 720
(2008/09/18)
-
- Solid-supported acids as mild and versatile reagents for the deprotection of aromatic ethers
-
Equation Presented p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found to be effective in cleaving aromatic ethers containing isopropyl, tert-butyl, allyl, and benzyl groups, as well as mono-, di-, and trimethoxylated benzyl groups, in moderate to excellent yields (54-95%). These protecting groups could be selectively deprotected when they were simultaneously present on the same or different aromatic rings in a substrate.
- Ploypradith, Poonsakdi,Cheryklin, Pannarin,Niyomtham, Nattisa,Bertoni, Daniel R.,Ruchirawat, Somsak
-
p. 2637 - 2640
(2008/02/08)
-
- Competitive formation of β-amino acids, propenoic, and ylidenemalonic acids by the Rodionov reaction from malonic acid, aldehydes, and ammonium acetate in alcoholic medium
-
The Rodionov reaction of 49 available aliphatic and aromatic aldehydes with malonic acid and ammonium acetate in alcoholic medium, resulting in formation of β-amino acids, propenoic, and ylidenemalonic acids, was studied. Certain regioselectivity regularities of the reaction were revealed. Among the variety of ketones studied, cyclohexanone is the only whose reaction yields a β-amino acid. Unusual dehydrofluorination of 6-chloro-2-fluorocinnamic acid under the Rodionov reaction was discovered. 2005 Pleiades Publishing, Inc.
- Lebedev,Lebedeva,Sheludyakov,Kovaleva,Ustinova,Kozhevnikov
-
p. 1113 - 1124
(2007/10/03)
-
- Chemistry of renieramycins. Part 4. Synthesis of a simple natural marine product, 6-hydroxy-7-methoxyisoquinolinemethanol
-
6-Hydroxy-7-methoxyisoquinolinemethanol (15) and mimosamycin (1) were recently isolated from a marine sponge, Haliclona sp. The former was prepared in ten steps from vanillin (22) in 26% overall yield using an isopropyl for phenol protection.
- Saito, Naoki,Tanaka, Chieko,Satomi, Tomoo,Oyama, Chigusa,Kubo, Akinori
-
p. 282 - 286
(2007/10/03)
-
- Convergent total synthesis of lamellarin K
-
The azomethine ylide derived from dihydroisoquinolinium salt 24 undergoes an intramolecular [3 + 2] cycloaddition reaction to give pyrrole 25 which upon de-isopropylation affords the marine alkaloid lamellarin K 4.
- Banwell, Martin,Flynn, Bernard,Hockless, David
-
p. 2259 - 2260
(2007/10/03)
-
- Synthetic studies on naturally occurring coumarins. II. Synthesis of 6,7-dimethoxy- and 7,8-dimethoxy-5-[(E)-3-oxo-1-butenyl]coumarins
-
In connection with studies on the structure elucidation of the so-called Reisch's coumarin isolated from Toddalia asiatica, syntheses of two coumarins (4 and 5) were accomplished via the routes shown in Charts 2 and 3, respectively. Melting points and NMR data of the synthesized coumarins (4 and 5) and of related coumarins (5-methoxysuberenon, toddalenone, and Reisch's coumarin) are given in Table I, suggesting that so-called Reisch's coumarin might be 4.
- Ishii,Ishikawa,Wada,Miyazaki,Kaneko,Harayama
-
p. 2614 - 2619
(2007/10/02)
-
- BASIC INTRAMOLECULAR ACYLATION. SYNTHESIS OF 2-ARYL-1-TETRALONES BEARING ISOPROPOXY OR BENZYLOXY GROUPS, SYNTHETIC KEY INTERMEDIATES FOR PHENOLIC ANTILEUKAEMIC BENZOPHENANTRIDINE ALKALOIDS, FROM 2,4-DIARILBUTYRIC ACID DERIVATIVES
-
Generally applicable intramolecular cyclisation of 2,4-diarylbutyric acids having isopropoxy (4) or benzyloxy (12) groups used to protect phenolic functions was required for the purpose of synthesis of phenolic benzophenantridine alkaloids.Treatment of the butyric acids (4b), (4d), (4f), and (12) with POCl3 in acetonitrile in the presence of potassium carbonate furnished the corresponding tetralones (5b), (5d), (5f), and (13) in excellent yield, respectively, without the cleavage of its isopropoxy or benzyloxy groups.A plausible mechanism for basic intramolecular acylation using POCl3 is proposed.
- Ishii, Hisashi,Chen, Ih-Sheng,Ueki, Satoshi,Masuda, Takeshi,Morita, Kenji,Ishikawa, Tsutomu
-
p. 2415 - 2420
(2007/10/02)
-
- Direct Synthesis of Benzophenanthridines and Benzophenanthridones via SRN1 Reactions
-
A straightforward and high-yield route to the 11,12-dihydrobenzophenanthridine (3) and 11,12-dihydrobenzophenanthridone (14) ring systems is based upon an SRN1 reaction between 2-halobenzylamines 1 or 2-halobenzoic acids 11 and enolates derived from tetralones 2.The efficient dehydrogenation of 3 or 14 gives the benzophenthridines 4 or benzophenanthridones 15.Use of properly substituted reactants leads to nitidine, avicine, and fagaronine and to analogues of those natural products.
- Beugelmans, Rene,Chastanet, Jacqueline,Ginsburg, Helene,Quintero-Cortes, Leticia,Roussi, Georges
-
p. 4933 - 4938
(2007/10/02)
-
- Synthesis and Antitumor Activity of Structural Analogues of the Anticancer Benzophenanthridine Alkaloid Fagaronine Chloride
-
The indenoisoquinoline analogue 4 of fagaronine chloride (2) has been prepared, as well as its positional isomer 20 and the corresponding mesylated derivatives 16 and 19.Compounds 4, 16, and 20 were tested against P388 lymphocytic leukemia and found to possess significant activity.A tricyclic analogue 24 was also synthesized and was devoid of cytotoxicity in the KB cancer cell culture system.The change in the substitution pattern of the A-ring on going from 4 to 20 was tolerated without producing a significant decrease in antitumor activity.
- Cushman, Mark,Mohan, Prem
-
p. 1031 - 1036
(2007/10/02)
-
- In vitro metabolism of 4-benzylisoquinolines, analogs of papaverine
-
A comparative study was made on sliced Rat liver of the in vitro disappearance of papaverine, PV 2 6,7-dimethoxy-4-(parachlorobenzyl)isoquinoline and its mono and di isopropoxy derivatives. Data show that papaverine and PV 2 are equally sensitive to oxygenases, although 7 mono and 6,7 di-isopropoxy derivatives are much less so, being more bulky and undergo in enzymic O-dealkylation less easily. The data also show that PV 2 and 6-isopropoxy desmethoxy PV 2 disappear at the same rate, more readily than the 7 isopropoxy isomer. This confirms the in vivo results previously reported. The antispasmodic in vitro activity of these compounds is reported.
- Coulomb,Lussiana,Plat,Viel,Midol-Monnet
-
p. 957 - 977
(2007/10/02)
-