- Discovery of Novel Bacterial Chalcone Isomerases by a Sequence-Structure-Function-Evolution Strategy for Enzymatic Synthesis of (S)-Flavanones
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Chalcone isomerase (CHI) is a key enzyme in the biosynthesis of flavonoids in plants. The first bacterial CHI (CHIera) was identified from Eubacterium ramulus, but its distribution, evolutionary source, substrate scope, and stereoselectivity are still unclear. Here, we describe the identification of 66 novel bacterial CHIs from Genbank using a novel Sequence-Structure-Function-Evolution (SSFE) strategy. These novel bacterial CHIs show diversity in substrate specificity towards various hydroxylated and methoxylated chalcones. The mutagenesis of CHIera according to the substrate binding models of these novel bacterial CHIs resulted in several variants with greatly improved activity towards these chalcones. Furthermore, the preparative scale conversion catalyzed by bacterial CHIs has been performed for five chalcones and revealed (S)-selectivity with up to 96 % ee, which provides an alternative biocatalytic route for the synthesis of (S)-flavanones in high yields.
- Bornscheuer, Uwe T.,Brückner, Stephan I.,Gei?ler, Torsten,Gross, Egon,Hartmann, Beate,Ley, Jakob P.,Meinert, Hannes,R?ttger, Carsten,Schuiten, Eva,Yi, Dong,Zirpel, Bastian
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supporting information
p. 16874 - 16879
(2021/07/06)
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- Chiral separation of novel iminonaringenin derivatives
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A series of 4-iminonaringenin derivatives 2-6 have been prepared in good overall yields from a condensation reaction between naringenin and primary amines. The structures of all products were confirmed by ultraviolet, infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques. These derivatives were analyzed by high-performance liquid chromatography using polysaccharide-based chiral stationary phases, namely, Chiralpak IB and Chiralcel OD, using various mobile phases. 2-Propanol showed a high enantioselectivity for naringin and its derivatives using achiral column containing immobilized polysaccharides (Chiralpak IB).
- Bouanini, Meriem,Belboukhari, Nasser,Menéndez, J. Carlos,Sekkoum, Khaled,Cheriti, Abdelkarim,Aboul-Enein, Hassan Y.
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p. 484 - 490
(2018/04/02)
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- 5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one (naringenin): X-ray diffraction structures of the naringenin enantiomers and DFT evaluation of the preferred ground-state structures and thermodynamics for racemization
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The R- and S-enantiomers of naringenin were separated by chiral supercritical fluid (SCF) and the absolute configuration of each enantiomer was established by X-ray crystallography. The solid-state data is in agreement with the reported circular dichroism spectra. Both enantiomers crystallize in the monoclinic crystal system in the space group P21 with two independent molecules in the asymmetric unit. In all molecules, the pyrone ring adopts a flattened chair-like conformation in which the C1 atom deviates from the plane drawn through the remaining five atoms of this heterocycle. The 4-hydroxyphenyl substituent located at C1 of the pyrone ring occupies an equatorial position and lies in a plane that is almost perpendicular to the aromatic platform associated with the heterocyclic portion of the molecule. Strong intramolecular O-H?O hydrogen bonding exists between the carbonyl moiety and the aryl hydroxyl group at C5. In both enantiomers, a favorable mutual orientation of two independent molecules promotes the formation of intermolecular O-H?O hydrogen bonds that link them into dimers. There are additional long-range intermolecular O-H?O hydrogen bonds and weak C-H?O contacts within the unit cell of each enantiomer that connect dimers in an extended network. DFT calculations have been performed and the thermodynamics for naringenin racemization via an acyclic chalcone have been computed. Eight energetically accessible conformations have been verified for S-naringenin.
- Nesterov, Volodymyr V.,Zakharov, Lev N.,Nesterov, Vladimir N.,Calderon, Jose G.,Longo, Antonella,Zaman, Khadiza,Choudhury, Feroza Kaneez,Farrell, William,Shulaev, Vladimir,Richmond, Michael G.
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p. 994 - 1000
(2016/12/18)
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- Enantioselective modulatory effects of naringenin enantiomers on the expression levels of miR-17-3p involved in endogenous antioxidant defenses
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Naringenin is a flavanone present in citrus fruit as a mixture of chiral isomers. The numerous biological properties attributed to this compound include antioxidant and anti-inflammatory activities, even though the molecular mechanisms of these remain unknown. This study aims to evaluate the effects of racemic and enantiomeric naringenin on the expression levels of miR-17-3p, miR-25-5p and relative mRNA targets, to elucidate the mechanisms underlying these antioxidant and anti-inflammatory properties. Caco-2 cells, a well characterized in vitro model which mimics the intestinal barrier, were treated with subtoxic concentrations of racemate and enantiomers. The expression levels of miR-17-3p and miR-25-5p were determined by Real-Time PCR and were found to be decreased for both miRNAs. miR-17-3p behavior was in agreement with the increased levels of target mRNAs coding for two antioxidant enzymes, manganese-dependent superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPx2), while expression levels of miR-25-5p were not in agreement with its target mRNAs, coding for two pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6). These results lead to the conclusion that naringenin could exert its antioxidant activity through epigenetic regulation operated by miRNAs, while anti-inflammatory activity is regulated by other miRNAs and/or mechanisms.
- Curti, Valeria,Di Lorenzo, Arianna,Rossi, Daniela,Martino, Emanuela,Capelli, Enrica,Collina, Simona,Daglia, Maria
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- Functionalities tuned enantioselectivity of phenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC
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The mixed chloro- and methyl- functionalities can greatly modulate the enantioselectivities of phenylcarbamate cyclodextrin (CD) clicked chiral stationary phases (CSPs). A comparison study is herein reported for per(4-chloro-3-methyl)phenylcarbamate and per(2-chloro-5-methyl)phenylcarbamate β-CD clicked CSPs (i.e., CCC4M3-CSP and CCC2M5-CSP). The enantioselectivity dependence on column temperature was studied in both normal-phase and reversed-phase mode high performance liquid chromatography (HPLC). The thermodynamic study revealed that the stronger intermolecular interactions can be formed between CCC4M3-CSP and chiral solutes to drive the chiral separation. The higher enantioselectivities of CCC4M3-CSP were further demonstrated with the enantioseparation of 17 model racemates in HPLC.
- Tang, Jian,Lin, Yuzhou,Yang, Bo,Zhou, Jie,Tang, Weihua
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p. 566 - 573
(2017/08/26)
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- Biomimetic synthesis and HPLC-ECD analysis of the isomers of dracocephins A and B
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Starting from racemic naringenin ((±)-1), a mixture of dracocephin A stereoisomers 6-(2″-pyrrolidinone-5″-yl)naringenin (±)-2a-d and its regioisomer, dracocephin B 8-(2″-pyrrolidinone-5″-yl)naringenin (±)-3a-d originally isolated from Dracocephalum rupestre, have been synthesized in a one-pot reaction. The separation of 2a-d and 3a-d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC-ECD measurements and TDDFT-ECD calculations. The synthesized flavonoid alkaloids were further characterized by physicochemical and in vitro pharmacological studies.
- Ilkei, Viktor,Spaits, András,Prechl, Anita,Szigetvári, áron,Béni, Zoltán,Dékány, Miklós,Szántay, Csaba,Müller, Judit,K?ncz?l, árpád,Szappanos, ádám,Mándi, Attila,Antus, Sándor,Martins, Ana,Hunyadi, Attila,Balogh, Gy?rgy Tibor,Kalaus, Gy?rgy,B?lcskei, Hedvig,Hazai, László,Kurtán, Tibor
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p. 2523 - 2534
(2016/12/07)
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- An eco-friendly enantioselective access to (R)-naringenin as inhibitor of proinflammatory cytokine release
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(RS)-Naringenin is a flavanone well-known for its beneficial health-related properties, such as its anti-inflammatory activity. The preparative enantioselective chromatographic resolution of commercial (RS)-naringenin was performed on a Chiralpak AD-H column (500×50 mm i.d., dp 20 μm) using MeOH as eluent. The developed method is in accordance with the principles of green chemistry, since the environmental impact was lowered by recycling of the eluent, and allowed the production of gram amounts of each enantiomer with high purity (chemical purity >99%, enantiomeric excess (ee) >94%). Racemic and enantiomeric naringenin were subjected to an exhaustive in vitro investigation of anti-inflammatory activity, aimed at evaluating the relevance of chirality. The assay with cultured human peripheral blood mononuclear cells (hPBMC) activated by phytohemagglutinin A revealed that (R)-naringenin was more effective in inhibiting T-cell proliferation than the (S)-enantiomer and the racemate. Moreover, (R)-naringenin significantly reduced proinflammatory cytokine levels such as those of TNF-α and, with less potency, IL-6. These results evidenced the anti-inflammatory potential of naringenin and the higher capacity of (R)-naringenin to inhibit both in vitro hPBMC proliferation and cytokine secretion at non toxic doses. Thus, (R)-naringenin is a promising candidate for in vivo investigation. Copyright
- Gaggeri, Raffaella,Rossi, Daniela,Daglia, Maria,Leoni, Flavio,Avanzini, Maria Antonia,Mantelli, Melissa,Juza, Markus,Collina, Simona
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p. 1531 - 1538
(2013/09/12)
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- Enantiomers of naringenin as pleiotropic, stereoselective inhibitors of cytochrome P450 isoforms
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Interactions between naringenin and the cytochrome P450 (CYP) system have been of interest since the first demonstration that grapefruit juice reduced CYP3A activity. The effects of naringenin on other CYP isoforms have been less investigated. In addition
- Lu, Wenjie Jessie,Ferlito, Valentina,Xu, Cong,Flockhart, David Alastair,Caccamese, Salvatore
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experimental part
p. 891 - 896
(2012/07/13)
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- Medicinal flowers. xxvii.1) New flavanone and chalcone glycosides, arenariumosides i, ii, iii, and iv, and tumor necrosis factor-α inhibitors from everlasting, flowers of helichrysum arenarium
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The methanolic extract from the flowers of Helichrysum arenarium L. Moench was found to show inhibitory effect on tumor necrosis factor-α (TNF-α, 1 ng/ml)-induced cytotoxicity in L929 cells. From the methanolic extract, 50 constituents including four new
- Toshio Morikawa,Li-Bo Wang,Seikou Nakamura,Kiyofumi Ninomiya,Eri Yokoyama,Hisashi Matsuda,Osamu Muraoka,Li-Jun Wu,Yoshikawa, Masayuki
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experimental part
p. 361 - 367
(2009/12/26)
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- Site-specific fluorescent labeling approaches for naringenin, an essential flavonone in plant nitrogen-fixation signaling pathways
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(Chemical Equation Presented) In search of an appropriate position for the fluorescent labeling, six chemically available positions of the flavonone core of naringenin have been examined. A number of azido-containing naringenin derivatives were accordingly prepared in various site-specific fashions, and the mild Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition successfully served as the common "Click" labeling tool in the final steps. On the basis of the biological activities of the first batch of labeled compounds, further optimization at the C-6 position of naringenin finally afforded naringenin-flu (27), which acquired 20% of the potency of naringenin and presented good optical properties. Entry of naringenin-flu into living Rhizobium cells was demonstrated by in vitro fluorescent imaging experiments.
- Chen, Lei,Li, Feng-Qing,Hou, Bi-He,Hong, Guo-Fan,Yao, Zhu-Jun
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supporting information; experimental part
p. 8279 - 8285
(2009/04/11)
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