المؤلفون: Liu-Bing Hu, Hong-Hong Qiu, Man-Mei Li, Wang Yifei, Liang-Shun Fu, Peng-Chao Zhang, Yan Wang, Min Liu, Zhong Liu

المصدر: Medicinal Chemistry Research. 29:942-953

مصطلحات موضوعية: biology, 010405 organic chemistry, Chemistry, Endoplasmic reticulum, Organic Chemistry, medicine.disease, biology.organism_classification, 01 natural sciences, 0104 chemical sciences, Hsp90 inhibitor, Metastasis, HeLa, 010404 medicinal & biomolecular chemistry, Cancer research, Unfolded protein response, medicine, General Pharmacology, Toxicology and Pharmaceutics, Signal transduction, Protein kinase B, PI3K/AKT/mTOR pathway

الوصف: Patients with advanced-stage cervical cancer have a high rate of morbidity and mortality, predominantly due to the metastasis of cervical cancer cells. Therefore, the development of novel agents to prevent metastasis is required for improved cervical cancer therapeutics. SNX-2112, a potent and selective Hsp90 inhibitor, is an anticancer candidate in clinical trials for the treatment of some solid tumors and lymphomas. However, the effects of SNX-2112 on the migration and invasion of cervical cancer cells are unclear. This study aimed at exploring the effects of SNX-2112 on the migration and invasion of cervical cancer cells and revealing the underlying molecular mechanisms. We found that SNX-2112 significantly decreased the viability, colony formation ability, and migration of HeLa and U14 cells. The invasiveness of HeLa cells and the proteins involved in metastasis were markedly reduced after SNX-2112 treatment. SNX-2112 inactivated the focal adhesion kinase (FAK) and inhibited the expression levels of matrix metallopeptidase (MMP)-9, MMP-2, SLUG, SNAIL, β-catenin, and Vimentin. Furthermore, SNX-2112 inhibited the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in HeLa cells by decreasing the phosphorylation of Akt, mTOR, S6, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). It also reduced the expression levels of the endoplasmic reticulum (ER)-localized molecular chaperones, Calnexin and BiP, and unfolded protein response (UPR)-related proteins IRE1α and PERK, suggesting that SNX-2112 can suppress ER stress and thus, inactivate the UPR in HeLa cells. Taken together, these findings indicate that SNX-2112 may efficiently suppress the proliferation, migration, and invasion of cervical cancer cells by inhibiting the Akt/mTOR pathway and could serve as a candidate drug for the treatment of human cervical cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::32931e4604e444513226eb72c5ac20b5Test
https://doi.org/10.1007/s00044-020-02534-3Test

المؤلفون: Ying Wang, Wen-Cai Ye, Wen Cheng, Jian-Guo Song, Xiao-Jun Huang, Ren-Wang Jiang, Man-Mei Li, Yao-Lan Li, Jun-Cheng Su, Yuan-Lin Zhong

المصدر: Journal of Natural Products. 82:2818-2827

مصطلحات موضوعية: Pharmacology, Euphorbia, biology, 010405 organic chemistry, Chemistry, medicine.drug_class, Stereochemistry, Chemical shift, Organic Chemistry, Pharmaceutical Science, Nuclear magnetic resonance spectroscopy, Ring (chemistry), biology.organism_classification, 01 natural sciences, Nmr data, Anti-inflammatory, 0104 chemical sciences, Analytical Chemistry, 010404 medicinal & biomolecular chemistry, Complementary and alternative medicine, Drug Discovery, Proton NMR, medicine, Molecular Medicine, Euphorbia helioscopia

الوصف: Guided by 1H NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (1-11) were isolated from the aerial parts of Euphorbia helioscopia. Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound 1 is the third member thus far of a rare class of Euphorbia diterpenes featuring an unusual 5/10 fused ring system, and 2-4 are new jatrophane diterpenes. Based on the NMR data of the jatrophane diterpenes obtained in this study as well as those with crystallographic structures reported in the literature, the correlations of the chemical shifts of the relevant carbons and the configurations of C-2, C-13, and C-14 of their flexible macrocyclic ring were considered. Moreover, the anti-inflammatory activities of 1-11 were investigated by monitoring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Compound 1 showed an IC50 of 7.4 ± 0.6 μM, which might be related to the regulation of the NF-κB signaling pathway by suppressing the translocation of the p65 subunit and the consequent reduction of IL-6 and TNF-α secretions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::5eb703095226e62cc0b47eb490712253Test
https://doi.org/10.1021/acs.jnatprod.9b00519Test

المؤلفون: Wei Tang, Li-Jun Hu, Jing Lu, Ying Wang, Shao-Min Yang, Yao-Lan Li, Wen-Cai Ye, Man-Mei Li, Li-Feng Chen, Dong-Mei Zhang, Qiao-Yun Song

مصطلحات موضوعية: Human cytomegalovirus, viruses, virus diseases, RNA, Outbreak, Biology, medicine.disease, medicine.disease_cause, Virology, Small molecule, Virus, chemistry.chemical_compound, Herpes simplex virus, chemistry, medicine, DNA, Coronavirus

الوصف: The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1H-xanthene-1,3(2H)-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::bdbcd7ea210c9e2b55ebe625a20bf7f9Test
https://doi.org/10.1101/2020.11.14.382770Test

المؤلفون: Yu-Bo Zhang, Guo-Cai Wang, Neng-Hua Chen, Yao-Lan Li, Mo-Jiao Li, Zhong-Nan Wu, Wei Tang, Man-Mei Li, Ling Zhuang

المصدر: Phytochemistry. 137:81-86

مصطلحات موضوعية: medicine.drug_class, Stereochemistry, Anti-Inflammatory Agents, Plant Science, Asteraceae, Horticulture, Sesquiterpene, 01 natural sciences, Biochemistry, Anti-inflammatory, Mice, chemistry.chemical_compound, Ic50 values, medicine, Animals, Molecular Biology, Molecular Structure, biology, Plant Extracts, 010405 organic chemistry, General Medicine, biology.organism_classification, Elephantopus mollis, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, RAW 264.7 Cells, chemistry, Molephantin, Sesquiterpenes, Two-dimensional nuclear magnetic resonance spectroscopy

الوصف: Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 μM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 μM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a21d4e8562ba4fb0a41ab37a7965a17Test
https://doi.org/10.1016/j.phytochem.2017.01.020Test

المؤلفون: Yao-Lan Li, Xu-Hui Xiao, Man-Mei Li, Wen-Jun Song, Zhong Liu, Wei Tang, Li-Feng Chen, Ling Zhuang, Yu-Bo Zhang, Guo-Cai Wang

المصدر: Journal of Agricultural and Food Chemistry. 65:3481-3489

مصطلحات موضوعية: 0301 basic medicine, Rhodomyrtus tomentosa, Myrtaceae, Inflammation, Respiratory Syncytial Virus Infections, 03 medical and health sciences, medicine, Humans, Interleukin 6, biology, Cyclohexanones, Interleukin-6, Plant Extracts, Tumor Necrosis Factor-alpha, NF-kappa B, General Chemistry, biology.organism_classification, Virology, Molecular biology, In vitro, Respiratory Syncytial Viruses, IκBα, 030104 developmental biology, Real-time polymerase chain reaction, Fruit, biology.protein, Phosphorylation, I-kappa B Proteins, medicine.symptom, Thioredoxin, Reactive Oxygen Species, General Agricultural and Biological Sciences

الوصف: Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 ± 1.6 μM. Enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor κB (NF-κB) activation by suppressing IκBα phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-κB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced inflammation via the suppression of ROS-sensitive inflammatory signaling.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e87b5bc6bd5fe859e76b081f2135c7e9Test
https://doi.org/10.1021/acs.jafc.7b00537Test

المؤلفون: Zhu Yang, Man-Mei Li, Sangwei Lu, Yao-Lan Li, Ning Liang, Wei Tang, Yujun Liu, Yanxiang Zhao, Fenyong Liu, Shuai Wu

المصدر: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(3)

مصطلحات موضوعية: 0301 basic medicine, Male, medicine.drug_class, viruses, Gene Expression, Drug resistance, Respiratory Syncytial Virus Infections, Biology, Biochemistry, Antiviral Agents, Virus, Cell Line, Cell membrane, Small Molecule Libraries, 03 medical and health sciences, Mice, 0302 clinical medicine, Viral entry, Genetics, medicine, Animals, Respiratory system, Medicine, Chinese Traditional, Molecular Biology, Lung, Mice, Inbred BALB C, Research, Cell Membrane, virus diseases, respiratory system, Fusion protein, Virology, 030104 developmental biology, medicine.anatomical_structure, Cell culture, Respiratory Syncytial Virus, Human, Antiviral drug, Viral Fusion Proteins, 030217 neurology & neurosurgery, Biotechnology

الوصف: Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti-RSV activity of a small molecule, (1S,3R,4R,5R)-3,4- bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-1,5-dihydroxycyclohexane-1-carboxylic methyl ester (3,4-DCQAME) or 3,4- O-Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4-DCQAME potently inhibits RSV entry and infection. In vitro, 3,4-DCQAME can interact with F(ecto), the ectodomain of RSV fusion (F) protein. In cultured cells, the compound can block the interaction of F(ecto) protein with the cellular membrane and inhibit viral fusion during RSV entry, leading to inhibition of viral gene expression and infection. In RSV-infected mice that were treated with 3,4-DCQAME, we observed a reduction of RSV-induced pathologic changes and substantial inhibition of viral infection and growth in the lung tissues. Our results provide the first direct evidence of the anti-RSV activity of 3,4-DCQAME. Furthermore, these results suggest that 3,4-DCQAME represents a promising lead compound for anti-RSV therapeutic development.-Tang, W., Li, M., Liu, Y., Liang, N., Yang, Z., Zhao, Y., Wu, S., Lu, S., Li, Y., Liu, F. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b500ed94956649079a5421e3bfb01f9Test
https://pubmed.ncbi.nlm.nih.gov/30571312Test

المؤلفون: Wen Cheng, Guo-Cai Wang, Yu-Bo Zhang, Yao-Lan Li, Guang-Kai Kuang, Ding Luo, Man-Mei Li, Li-Jun He, Li Yang

المصدر: Journal of natural products. 81(10)

مصطلحات موضوعية: Hepatitis B virus, Magnetic Resonance Spectroscopy, Spectrophotometry, Infrared, Stereochemistry, Pharmaceutical Science, medicine.disease_cause, Cleavage (embryo), 01 natural sciences, Antiviral Agents, Plant Roots, Mass Spectrometry, Analytical Chemistry, chemistry.chemical_compound, Alkaloids, Matrine, X-Ray Diffraction, Drug Discovery, medicine, Matrines, Pharmacology, Sophora flavescens, biology, Molecular Structure, 010405 organic chemistry, Alkaloid, Organic Chemistry, Nuclear magnetic resonance spectroscopy, biology.organism_classification, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Complementary and alternative medicine, chemistry, Molecular Medicine, Spectrophotometry, Ultraviolet, Piperidine, Sophora, Quinolizines

الوصف: Eight new matrine-type alkaloids, flavesines G-J (1-4), alopecurine B (5), 7,11-dehydro-oxymatrine (6), 10-oxy-5,6-dehydromatrine (7), and 10-oxysophoridine (8), along with nine known analogues (9-17) were isolated from the roots of Sophora flavescens. Compounds 1-3 are the first natural matrine-type alkaloids with an open-loop ring D, while compound 4 represents an unprecedented dimerization pattern constructed from matrine and piperidine, and 5 is the first example of a matrine-type alkaloid with cleavage of the C-5-C-6 bond. The new structures were elucidated by means of spectroscopic data analysis (including NMR, MS, IR, and UV), and the absolute configurations were determined using single-crystal X-ray diffraction and ECD data. The isolated alkaloids were evaluated for their antiviral activity against hepatitis B virus, and compounds 1, 4, 5, 10, and 14 exhibited comparable antiviral potencies to matrine.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::601c379a92bfac733b178e8d715e75b2Test
https://pubmed.ncbi.nlm.nih.gov/30298740Test

المؤلفون: Man-Mei Li, Wang Yifei, Hui Wang, Yuxiao Zou, Fang Ma, Wenwei Shen, Yao-Lan Li, Xiao-Qi Zhang

المصدر: Biological & Pharmaceutical Bulletin. 39:1667-1674

مصطلحات موضوعية: Gene Expression Regulation, Viral, 0301 basic medicine, Cell Survival, Herpesvirus 2, Human, viruses, Pharmaceutical Science, Herpesvirus 1, Human, Biology, Virus Replication, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, Chlorocebus aethiops, Stilbenes, Gene expression, medicine, Animals, Humans, Vero Cells, Gene, Flavonoids, Pharmacology, Mulberrofuran G, Regulation of gene expression, NF-kappa B, NF-κB, DNA, General Medicine, Molecular biology, Plant Leaves, 030104 developmental biology, Herpes simplex virus, chemistry, Vero cell, Morus, HeLa Cells

الوصف: Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3'-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC50 values of 2.2, 1.5 and 2.5 µg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles. Following viral penetration, Kuwanon X reduced the expression of HSV-1 IE and L genes, and decreased the synthesis of HSV-1 DNA. Furthermore, it was demonstrated that Kuwanon X inhibited the HSV-1-induced nuclear factor (NF)-κB activation through blocking the nuclear translocation and DNA binding of NF-κB. These results suggest that Kuwanon X exerts anti-HSV activity through multiple modes and could be a potential candidate for the therapy of HSV infection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff69ad8554f4c6d3a11904b8b04f4c29Test
https://doi.org/10.1248/bpb.b16-00401Test

المؤلفون: Yan-Yan Ma, Yan Wang, Hongyuan Chen, Liang-Shun Fu, Min Liu, Man-Mei Li, Xuyan Tian, Wang Yifei, Xiao Liu, Hong-Tao Sun, Zhong Liu, Peng-Chao Zhang

المصدر: Biochemical Pharmacology. 172:113771

مصطلحات موضوعية: Vascular Endothelial Growth Factor A, Indazoles, Cell Survival, Angiogenesis, Mice, Nude, Antineoplastic Agents, Breast Neoplasms, medicine.disease_cause, Biochemistry, Hsp90 inhibitor, Mice, Cell Movement, Cell Line, Tumor, VEGF Signaling Pathway, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, HSP90 Heat-Shock Proteins, Protein kinase B, PI3K/AKT/mTOR pathway, Pharmacology, Tube formation, Molecular Structure, Neovascularization, Pathologic, Chemistry, Cancer, Neoplasms, Experimental, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Gene Expression Regulation, Neoplastic, Cancer research, Female, Carcinogenesis

الوصف: The inhibition of angiogenesis is suggested to be an attractive strategy for cancer therapeutics. Heat shock protein 90 (Hsp90) is closely related to tumorigenesis as it regulates the stabilization and activated states of many client proteins that are essential for cell survival and tumor growth. Here, we investigated the mechanism whereby AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and tumor angiogenesis. Based on our results, AT-533 suppressed the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs), and was more effective than the Hsp90 inhibitor, 17-AAG. Furthermore, AT-533 inhibited angiogenesis in the aortic ring, Matrigel plug, and chorioallantoic membrane (CAM) models. Mechanically, AT-533 inhibited the activation of VEGFR-2 and the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK, in HUVECs, and the viability of breast cancer cells and the HIF-1α/VEGF signaling pathway under hypoxia. In vivo, AT-533 also inhibited tumor growth and angiogenesis by inducing apoptosis and the HIF-1α/VEGF signaling pathway in breast cancer cells. Taken together, our findings indicate that the Hsp90 inhibitor, AT-533, suppresses breast cancer growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 may thus be a potentially useful drug candidate for breast cancer therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff31c96bd915836e7aa80f94c519c673Test
https://doi.org/10.1016/j.bcp.2019.113771Test

المؤلفون: Lei Wang, Jia-Qing Cao, Mu Chen, Ni-Ping Li, Yuan-Lin Zhong, Man-Mei Li, Yan Wu, Wen-Cai Ye

المصدر: Chemistrybiodiversity. 15(7)

مصطلحات موضوعية: Circular dichroism, Stereochemistry, Monoterpene, Myrtaceae, Phloroglucinol, Callistemon rigidus, Molecular Conformation, Bioengineering, Microbial Sensitivity Tests, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Antiviral Agents, Adduct, chemistry.chemical_compound, Structure-Activity Relationship, medicine, Simplexvirus, Molecular Biology, biology, Dose-Response Relationship, Drug, 010405 organic chemistry, Chemistry, Triketone, Stereoisomerism, General Chemistry, General Medicine, Ketones, biology.organism_classification, 0104 chemical sciences, NMR spectra database, Herpes simplex virus, Monoterpenes, Molecular Medicine

الوصف: Callistrilones F - K (1 - 6), six new triketone-phloroglucinol-monoterpene hybrids were isolated from the twigs and leaves of Callistemon rigidus. Their structures with absolute configurations were established by a combination analysis of NMR spectra, X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 3 and 4 exhibited moderate inhibitory activities against herpes simplex virus (HSV-1) with IC50 values of 10.00 ± 2.50 and 12.50 ± 1.30 μm, respectively.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4244369d0c859cd93044d4d3e536d402Test
https://pubmed.ncbi.nlm.nih.gov/29806969Test