520-33-2Relevant articles and documents
Discovery of Novel Bacterial Chalcone Isomerases by a Sequence-Structure-Function-Evolution Strategy for Enzymatic Synthesis of (S)-Flavanones
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
supporting information, p. 16874 - 16879 (2021/07/06)
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.
Design and synthesis of 7-O-1,2,3-triazole hesperetin derivatives to relieve inflammation of acute liver injury in mice
Zheng, Yan,Zhang, Yi-long,Li, Zeng,Shi, Wen,Ji, Ya-ru,Guo, Ya-Hui,Huang, Cheng,Sun, Guo-ping,Li, Jun
, (2021/01/25)
Based on the previous research results of our research group, to further improve the anti-inflammatory activity of hesperetin, we substituted triazole at the 7-OH branch of hesperetin. We also evaluated the anti-inflammatory activity of 39 new hesperetin derivatives. All compounds showed inhibitory effects on nitric oxide (NO) and inflammatory factors in lipopolysaccharide-induced RAW264.7 cells. Compound d5 showed a strong inhibitory effect on NO (half maximal inhibitory concentration = 2.34 ± 0.7 μM) and tumor necrosis factor-α, interleukin (IL)-1β, and (IL-6). Structure–activity relationships indicate that 7-O-triazole is buried in a medium-sized hydrophobic cavity that binds to the receptor. Compound d5 can also reduce the reactive oxygen species production and significantly inhibit the expression of inducible NO synthase and cyclooxygenase-2 through the nuclear factor-κB signaling pathway. In vivo results indicate that d5 can reduce liver inflammation in mice with acute liver injury (ALI) induced by CCI4. In conclusion, d5 may be a candidate drug for treating inflammation associated with ALI.
Enhanced antioxidant, anti-inflammatory and α-glucosidase inhibitory activities of citrus hesperidin by acid-catalyzed hydrolysis
Lu, Shengmin,Xing, Jianrong,Zheng, Meiyu
, (2020/08/05)
Hesperidin hydrolysates (HHS) was produced by the hydrolysis of hesperidin (HDN) in previous studies. The potential components in HHS were identified by LC-MS, and minor components (MCS) in HHS were isolated. Antioxidant activities by radical-scavenging capacities, reducing capacity and β-carotene-linoleate assay, anti-inflammatory effects by inhibiting NO production of RAW 264.7 cells, and α-glucosidase inhibitory effects of HDN, HHS, MCS and henperetin (HTN) were investigated in present study. HHS showed higher radical scavenging activities, higher reducing capacity, and higher inhibitory activity in the β-carotene-linoleate assay than HDN. HHS inhibited the production of NO and pro-inflammatory cytokines of RAW 264.7 cells more strongly than HDN. HHS also intensively inhibited α-glucosidase activity whereas HDN showed little activity. In addition, the effects of MCS on above activities showed it play a synergistic part with HTN. This work suggested that hydrolyzation of HDN enhance the activities, and provided valuable information on effective utilization of HDN.
Hesperetin as an inhibitor of the snake venom serine protease from Bothrops jararaca
dos Santos, Roney Vander,Grillo, Giovanna,Fonseca, Henrique,Stanisic, Danijela,Tasic, Ljubica
, p. 64 - 72 (2021/05/13)
The majority (90%) of the snakebite envenomation in Brazil accounts for Bothrops from the Viperidae family. Some snake venom serine proteases provoke blood coagulation in ophidian accident victims because of their fibrinolytic activity, one of those proteases from Bothrops jararaca (B. jararaca) has been chosen for this study. Our objectives were to isolate and characterize the target serine protease; isolate, purify, and characterize the orange bagasse flavone (hesperetin, Hst), and investigate the interactions between the targets, enzyme, and hesperetin. The purified serine protease was named BjSP24 because of its molecular mass and proteolytic activity. BjSP24 was folded and characterized using circular dichroism and showed low alpha-helix contents (7.7%). BjSP24 exhibited sequence similarity to other known snake venom serine proteases as measured in the enzyme tryptic peptides' LC-MS/MS run. Hesperetin was obtained within the expected yield and with the predominance of 2S isomer (82%). It acted as a mixed inhibitor for the serine protease (SVSP) from Bothrops jararaca snake venom observed in three different in vitro experiments, fluorescence, kinetics, and SSTD-NMR. It is still to determine if hesperetin might aid-in reverting the on site blood clotting problems just after snakebite accidents.
Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance
Tsunekawa, Ryuji,Katayama, Kazuhiro,Hanaya, Kengo,Higashibayashi, Shuhei,Sugimoto, Yoshikazu,Sugai, Takeshi
, p. 210 - 220 (2018/10/15)
3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI50). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI50 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI50 18 nm). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI50 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.
7-O-amido substituted hesperidin derivative and preparation method and application thereof
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Paragraph 0036-0041, (2019/11/12)
The invention discloses a 7-O-amido substituted hesperidin derivative and a preparation method and application thereof. The 7-O-amido substituted hesperidin derivative has the structural formula shownin a formula (I) (please see the specification for the formula (I)). Further pharmacological activity studies show that the related amido substituted hesperidin derivative can inhibit the release ofNO in a concentration dependency mode, production of inflammatory mediators of IL-6 and TNF-alpha is reduced, and compared with indomethacin and celecoxib, a compound 4d shows better inhibition of inflammatory activity, and significantly inhibits expression of nitric oxide synthase (iNOS) and COX-2; and the compound has the potential and value for development into anti-inflammatory drugs, and thecompound 4d is expected to be a candidate drug with the anti-inflammatory activity.
Design, synthesis and investigation of the potential anti-inflammatory activity of 7-O-amide hesperetin derivatives
Zhang, Yilong,Zheng, Yan,Shi, Wen,Guo, Yahui,Xu, Tao,Li, Zeng,Huang, Cheng,Li, Jun
, (2019/11/02)
To develop new anti-inflammatory agents, a series of 7-O-amide hesperetin derivatives was designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. All compounds showed inhibitory effect on LPS-induced NO production. Among them, 7-O-(2-(Propylamino)-2-oxoethyl)hesperetin (4d) and 7-O-(2-(Cyclopentylamino)-2-oxoethyl)hesperetin (4k) with hydrophobic side chains exhibited the most potent NO inhibitory activity (IC50 = 19.32 and 16.63 μM, respectively), showing stronger inhibitory effect on the production of pro- inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) than indomethacin and celecoxib at 10 μM. The structure-activity relationships (SARs) suggested that the 7-O-amide unit was buried in a medium-sized hydrophobic cavity of the bound receptor. Furthermore, compound 4d could also significantly suppress the expression of inducible nitric oxide synthase enzymes (iNOS) and cyclooxygenase-2 (COX-2), through the nuclear factor-kappa B (NF-κB) signaling pathway.
Design, synthesis and investigation of potential anti-inflammatory activity of O-alkyl and O-benzyl hesperetin derivatives
Huang, Ai-Ling,Zhang, Yi-Long,Ding, Hai-Wen,Li, Bo,Huang, Cheng,Meng, Xiao-Ming,Li, Jun
, p. 82 - 91 (2018/06/01)
Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compo
Functionalities tuned enantioselectivity of phenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC
Tang, Jian,Lin, Yuzhou,Yang, Bo,Zhou, Jie,Tang, Weihua
, p. 566 - 573 (2017/08/26)
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.
Enhanced antioxidant activity, antibacterial activity and hypoglycemic effect of luteolin by complexation with manganese(II) and its inhibition kinetics on xanthine oxidase
Dong, Hao,Yang, Xiaocui,He, Jiapeng,Cai, Sheng,Xiao, Kaijun,Zhu, Liang
, p. 53385 - 53395 (2017/12/02)
The present study aims to improve the biological activities of luteolin by complexation with manganese(ii). UV-visible spectroscopy, infrared spectroscopy, thermogravimetric analysis and elemental analysis were adopted to assess the relevant interaction of luteolin and manganese(ii) ions and the chelation sites. The antioxidant activity, hypoglycemic effect and antimicrobial activity of luteolin-manganese(ii) complex with respect to its parent luteolin and the inhibition effect of which on xanthine oxidase were investigated and compared. The spectroscopic data indicated that luteolin reacts with manganese(ii) cations through the chelation sites of 5-hydroxy and 4-carbonyl in two luteolin molecules. Antioxidant and antibacterial activity were enhanced after the complexation of manganese(ii) cations with luteolin. An inhibition effect assay found that luteolin and luteolin-manganese(ii) complex reversibly inhibited xanthine oxidase in a competitive manner. Luteolin-manganese(ii) complex had a more remarkable hypoglycemic effect than luteolin by increasing the glucose consumption in liver tissue.
