MOLECULES
·
2020
·Vol. 25
·期 3
·674
·
IF 3.267
Jie Liu,Xican Li,Rongxin Cai,Ziwei Ren,Aizhen Zhang,Fangdan Deng,Dongfeng Chen
To elucidate the mechanism of anti-ferroptosis and examine structural optimization in natural phenolics, cellular and chemical assays were performed with 2′-hydroxy chalcone butein and dihydroflavone (S)-butin. C11-BODIPY staining and flow cytometric assays suggest that butein more effectively inhibits ferroptosis in erastin-treated bone marrow-derived mesenchymal stem cells than (S)-butin. Butein also exhibited higher antioxidant percentages than (S)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe3+-reducing antioxidant power assay, Cu2+-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH•)-trapping assay. Their reaction products with DPPH•were further analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Butein and (S)-butin produced a butein 5,5-dimer (m/z542, 271, 253, 225, 135, and 91) and a (S)-butin 5′,5′-dimer (m/z542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (S)-butin (m/z542, 523, 433, 419, 415, 406, and 375). Therefore, we conclude that butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). Following this pathway, butein and (S)-butin yield both self-dimers and cross dimers. Butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. This can be attributed the decrease in π-π conjugation in butein due to saturation of its α,β-double bond and loss of its 2′-hydroxy group upon biocatalytical isomerization.Keywords:butein;(S)-butin;anti-ferroptosis;antioxidant;2′-hydroxy chalcone;isomerization
研究领域:
细胞生物学
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药物化学
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分析化学
✓ 已验证
DOI
PubMed
高影响因子
ELECTROANALYSIS
·
2016
·Vol. 29
·期 3
·835-842
·
IF 2.471
Zhengkun Xie,Yongmei Wu,Sheng Kai,Gaiping Li,Baoxian Ye
A novel electrochemically activated doped Ta 2 O 5 particles modified carbon paste electrode (EA-Ta 2 O 5 -CPE) was prepared and applied for selective and sensitive determination of chrysin. X-ray diffraction (XRD), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) techniques and cyclic voltammetry (CV) were used to characterize the Ta 2 O 5 particles and investigate the electrochemical response of the sensor. Compared with bare CPE, the doped Ta 2 O 5 modified electrode got much more porous by electrochemical treatment and exhibited larger effective surface area, more reactive site and excellent electrochemical catalytic activity toward the oxidation of chrysin. Under optimum conditions by LSV, the oxidation peak currents responded to chrysin linearly over a concentration range from 5.0×10 −8 to 7.0×10 −6 mol L −1 with a detection limit of 2.0×10 −8 mol L −1 (5.08 ng mL −1 ). The fabricated sensor showed anti-interference ability against the biological common interferents (i.e. baicalein, baicalin) and provided to be reliable for the determination of chrysin in Chinese medicinal herb Oroxylum indicum and chrysin capsules samples with satisfactory results.
研究领域:
分析化学
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药物分析
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产品关联
DOI
高影响因子
FITOTERAPIA
·
2016
·
IF 2.408
Wen-Jia Kang,Da-Hong Li,Tong Han,Lin Sun,Yan-Bin Fu,Chun-Mei Sai,Zhan-Lin Li,Hui-Ming Hua
Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones , flemiphilippinones B ( 1 ) and C ( 2 ), and one new pterocarpoid, demethylwedelolactone-11-methyl ether ( 3 ), together with 12 known compounds ( 4 - 15 ). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI 50 value of 14.12 μM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI 50 values of 1.91 and 2.58 μM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G 2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway.
研究领域:
药用植物化学
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肿瘤生物学
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细胞信号通路研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2020
·
IF 4.673
L. Ravithej Singh,Yu-Lin Chen,Yuan-Yuan Xie,Wei Xia,Xing-Wen Gong,Robert C. Hider,Tao Zhou
In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 μM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 μM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.
研究领域:
药物化学
·
生物化学
✓ 已验证
DOI
高影响因子
Chinese Herbal Medicines
·
2018
·
IF 0
Ding Liu,Yan-peng Li,Hong-xiu Shen,Yang Li,Jun He,Qi-zhi Zhang,Yun-mei Liu
Objective To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay , so as to investigate molecular structure-activity relationship with molecular docking . Methods Target products were synthesized with high yield by substitution reaction, hydrolysis reaction, esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation. Results 7- O -amino acids chrysin derivatives 6a – 6l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil (5-FU). Among these derivatives, compound 5b (IC 50 = 24.50 ± 2.26 µmol/L), 5k (IC 50 = 24.30 ± 2.19 µmol/L), and 6f (IC 50 = 24.61 ± 2.01 µmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5g (IC 50 = 13.15 ± 1.73 µmol/L) and 5j (IC 50 = 12.34 ± 1.25 µmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results. Conclusion Compounds 5b, 5d, 5g, 5j, 5k , and 6f showed good antiproliferative effects on specific tumor cells, and compound 5g should be researched further when according to molecular docking.
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
产品关联
DOI
FREE RADICAL BIOLOGY AND MEDICINE
·
2015
·
IF 5.736
Xiaomin Xia,Juanli Fu,Xiufang Song,Qiong Shi,Chuanyang Su,Erqun Song,Yang Song
Fulminant hepatic failure (FHF) is a lethal clinical syndrome characterized by the activation of macrophages and the increased production of inflammatory mediators . The purpose of this study was to investigate the effects of neohesperidin dihydrochalcone (NHDC), a widely-used low caloric artificial sweetener against FHF. An FHF experimental model was established in mice by intraperitoneal injection of D-galactosamine ( d -GalN) (400 mg/kg)/lipopolysaccharides (LPS) (10 μg/kg). Mice were orally administered NHDC for 6 continuous days and at 1 h before d -GalN/LPS administration. RAW264.7 macrophages were used as an in vitro model. Cells were pre-treated with NHDC for 1 h before stimulation with LPS (10 μg/ml) for 6 h. d -GalN/LPS markedly increased the serum transaminase activities and levels of oxidative and inflammatory markers, which were significantly attenuated by NHDC. Mechanistic analysis indicated that NHDC inhibited LPS-induced myeloid differentiation factor 88 (MyD88) and TIR-containing adapter molecule (TRIF)-dependent signaling. Transient transfection of TLR4 or MyD88 siRNA inhibited the downstream inflammatory signaling. This effect could also be achieved by the pretreatment with NHDC. The fluorescence microscopy and flow cytometry results suggested that NHDC potently inhibited the binding of LPS to TLR4 in RAW264.7 macrophages. In addition, the inhibitory effect of NHDC on LPS-induced translocation of TLR4 into lipid raft domains played an important role in the amelioration of production of downstream pro-inflammatory molecules. Furthermore, the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by NHDC inhibited TLR4 signaling. In conclusion, our results suggest that NHDC attenuates d -GalN/LPS-induced FHF by inhibiting the TLR4-mediated inflammatory pathway, demonstrating a new application of NHDC as a hepatoprotective agent.
研究领域:
免疫学
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肝病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Mengyao Jiang,Yu Yan,Chuanying Zhang,Haibing Liao,Mengfan Wang,Xin Peng
The interactions of two dihydrochalcones (naringin dihydrochalcone (NGDC) and neohesperidin dihydrochalcone (NHDC)) with bovine serum albumin (BSA) and their anti-glycation effects were studied utilizing multiple spectral methods and molecular simulation technique. The findings proved that NGDC/NHDC could use a static quenching mechanism to reduce the intrinsic fluorescence of BSA, and the interaction between NGDC/NHDC and BSA was a spontaneous behavior with the binding constant ranging from 10 4 to 10 5 M −1 . Furthermore, NGDC and NHDC mainly interacted with the site I (subdomain IIA) of BSA via hydrophobic interactions and hydrogen bonds, endorsed by molecular docking study. A conjoint analysis of circular dichroism, three-dimensional fluorescence, dynamic light scattering, and UV-vis absorption spectra confirmed that NGDC/NHDC could induce some alterations in the spatial conformation and microenvironment of BSA. Additionally, NGDC and NHDC inhibited the non-enzymatic glycation of BSA by decreasing the contents of advanced glycation end products (AGEs), trapping methylglyoxal/glyoxal and maintaining the stability of the natural conformation of the protein. Overall, these findings were highly beneficial in disclosing the interaction mechanisms between dihydrochalcones and BSA and providing valuable information for the application of dihydrochalcones as functional food ingredients.
研究领域:
生物化学
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分子生物学
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食品科学
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2021
·Vol. 8
·期 15
·2100749
·
IF 16.806
Meirong Song,Ying Liu,Tingting Li,Xiaojia Liu,Zhihui Hao,Shuangyang Ding,Pharkphoom Panichayupakaranant,Kui Zhu,Jianzhong Shen
The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α -mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram-positive bacteria, but also restore the susceptibility of colistin against Gram-negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.
研究领域:
药理学
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微生物学
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植物化学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Gan Xin,Xie Jingwen,Dong Zhaojun,Wu Yuna,Zeng Xiaoqing,Yang Zhenzhen,Liu Bo,Zhu Min,Wang Bozhen,Li Wulan,Wang Ledan,Zhang Huajie,Wu Jianzhang,Hu Yue
Background: Pyroptosis, a cell death process triggered by chemotherapy drugs, has
emerged as a highly promising mechanism for combating tumors in recent years. As the lead of
new drugs, natural products play an important role in the discovery of anticancer drugs. Compared
to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior
safety profile. Among a series of MFHNP molecular skeletons, this study found that only
benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity
of 1 remains to be improved.
Aims: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by
modifying the chalcone structure.
Methods: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis,
several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer
activity was tested by MTT assay, and morphological indications of pyroptosis were observed
in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore,
to improve the activity of the chalcone skeleton, the anticancer group 3,4,5-
trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed,
synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally,
a quantitative structure-activity relationship (QSAR) model was established using the
eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore.
Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular
mechanisms of pyroptosis induced by the active compound.
Results: α, β-unsaturated ketone was the functional group of the chalcone skeleton and played a
pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients
(R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these
compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was
found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing
the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft
tumors.
Conclusion: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis
axis and is a kind of promising pyroptosis inducer.
研究领域:
肿瘤学
·
药理学
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Meng Wang,Guoxiu Cao,Junjie Zhou,Jinyuan Cai,Xianjie Ma,Zhikun Liu,Xiaochao Huang,Hengshan Wang
Developing multitarget platinum(IV) prodrugs is an important strategy to attenuate cisplatin (CDDP) resistance in tandem with reduced toxicity. Herein, six novel ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and evaluated for their anti-proliferative activities. Among them, 16a displayed higher cytotoxicity toward the tested cancer cell lines and lower cytotoxicity toward the human normal cells than CDDP or the combined group. Mechanistic studies revealed that 16a efficiently induced DNA damage and initiated a mitochondria-dependent apoptosis pathway. Besides, 16a significantly triggered ferroptosis by down-regulating expression levels of nuclear factor erythroid 2-related factor 2, glutathione peroxidase 4, and solute carrier family 7 member 11. Further, 16a obtained superior in vivo anti-tumor efficiency than CDDP in CDDP-resistant pancreatic cancer xenograft models but showed no significant side effects. In summary, our study suggested that 16a acts via a different anti-cancer mechanistic pathway than CDDP and may therefore encompass a novel practical strategy for cancer treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2024
·
IF 1.9
Lin Shuai,Cai Hui,Song Xuemei
The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Guliang Yang,Chi-Chen Lin,Yiwen Yang,Li Yuan,Peilei Wang,Xiang Wen,Min-Hsiung Pan,Hui Zhao,Chi-Tang Ho,Shiming Li
Dietary choline and its containing foods are biotransformed to trimethylamine (TMA) via gut microbial metabolism. Subsequently, as an intermediate molecule, TMA is quickly transported and oxidized in the liver by hepatic flavin monooxygenases to form trimethylamine oxide (TMAO). TMAO was treated as a waste byproduct from choline metabolism, but recent convincing evidence demonstrated the association between the small molecule TMAO and inflammation-related diseases, including blood vessel inflammation and vascular diseases. The scope of this study is to investigate the preventive effect of nobiletin on TMAO-induced blood vessel inflammation. Our results from Western blot showed that the inhibition of TMAO-induced cardiovascular inflammation was correlated with nobiletin-mediated inhibitory effects on NF-κB and MAPK/ERK related pathways. More specifically, nobiletin prevented the oxidative damage of vascular sites (proximal aorta), inhibited the activity of MAPK/ERK, reduced the expression of NF-κB p65 and phospho-NF-κB p65, and consequently decreased the inflammatory response. Flow cytometry analyses showed that nobiletin decreased TMAO-induced apoptosis of HUVEC cells and counteracted TMAO-induced HUVEC cell proliferation. Results from HE staining and immunohistochemical results also showed that nobiletin reduced the degree of inflammation of the proximal aorta in Sprague–Dawley rats. In summary, nobiletin significantly reduced TMAO-induced vascular inflammation via inhibition of the NF-κB/MAPK pathways.
研究领域:
药理学
·
心血管疾病
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分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）