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[PMID]:29216958
[Au] Autor:Guesmi F; Ben Hadj AS; Landoulsi A
[Ad] Endereço:Laboratory of Biochemistry and Molecular Biology, Faculty of Sciences of Bizerte, University of Carthage, Zarzouna 7021, Tunisia.
[Ti] Título:Investigation of Extracts from Tunisian Ethnomedicinal Plants as Antioxidants, Cytotoxins, and Antimicrobials.
[So] Source:Biomed Environ Sci;30(11):811-824, 2017 Nov.
[Is] ISSN:0895-3988
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To determine the medicinal potential of various plants and their parts extracted with different solvents. METHODS: The total phenolic content of acetonitrile/water (60%-40%) (ACN/W) and aqueous (W) extract fractions was determined by high-performance liquid chromatography (HPLC), and terpenic compounds were detected by gas chromatography/mass spectrometry (GC/MS). Antioxidant activity of the samples was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and ß-carotene bleaching method. Cell viability was investigated by thiazolyl blue tetrazolium bromide [3-(4,5-dimethylthiazol)-2-yl 2,5-diphenyltetrazolium bromide] (MTT) assay. The mechanisms involved in cytotoxic activity were investigated in a murine macrophage cell line (RAW 264.7) and cancer lines. RESULTS: Our findings show that 11 plant species exhibited biological activity. In addition, moderate antibacterial activity was reported against one or more of the tested bacterial strains at two concentrations: 300 µg and 3 mg/disc. Furthermore, our data reveal that among all plants investigated, some extract and hydrophobic fractions were potent scavengers of the DPPH radical (6.78 µg/mL < EC50 < 8.55 µg/mL). Taken together, our results show that Nerium oleander (NOACN/W) and Pituranthos tortuosus (PTACN/W) were highly cytotoxic against RAW 264.7 cells with IC80 values of 0.36, and 1.55 µg/mL, respectively. In contrast, murine macrophage cell lines had low growth and were significantly sensitive to water extracts of Thymus hirtus sp. algeriensis (THW), Lavandula multifida (LMW), and ACN/W extract of Erica multiflora (EMACN/W) at doses > 400, 47.20, and 116.74 µg/mL, respectively. The current work demonstrates that RAW 264.7 cell proliferation was inhibited by samples in a dose-dependent manner. CONCLUSION: Our findings, validated through free radical scavenging activity, agar diffusion assay, and cytotoxicity of essential oils towards cancer cells, show that ethnomedicinal plants used in this work have a novel application as a tumor suppressor.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antineoplásicos Fitogênicos/farmacologia
Citotoxinas/farmacologia
Extratos Vegetais/farmacologia
Plantas Medicinais/química
[Mh] Termos MeSH secundário: Animais
Antibacterianos/química
Antineoplásicos Fitogênicos/química
Bactérias/efeitos dos fármacos
Compostos de Bifenilo
Linhagem Celular
Citotoxinas/química
Etnobotânica
Camundongos
Estrutura Molecular
Fenóis/química
Fenóis/farmacologia
Picratos
Extratos Vegetais/química
Terpenos/química
Terpenos/farmacologia
Tunísia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents, Phytogenic); 0 (Biphenyl Compounds); 0 (Cytotoxins); 0 (Phenols); 0 (Picrates); 0 (Plant Extracts); 0 (Terpenes); DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.3967/bes2017.109


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[PMID]:29254300
[Au] Autor:Khalid M; Bilal M; Hassani D; Iqbal HMN; Huang D
[Ad] Endereço:School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
[Ti] Título:Antimicrobial, antioxidant, cytotoxicity and LC-MS analyses of Aerva javanica: an ethnomedicinally important plant.
[So] Source:J Biol Regul Homeost Agents;31(4):963-969, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:In this study, Aerva javanica was used to extract the essential oil with notable medicinal activities. The chemical composition was investigated by high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC-MS). Ten major chemical compounds were identified as flavonoids derivatives, dihydroxylated and glycosylated metabolites. The antimicrobial, antioxidant, and cytotoxicity activities were tested using agar well-diffusion assay, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free-radical scavenging and linoleic acid oxidation assays and hemolytic assay against human erythrocytes (RBCs), respectively. Plant extracts exhibited different extents of antimicrobial activities against selected bacterial and fungal strains; however, the essential oil displayed potent antimicrobial activity against all the tested strains. The percentage inhibition of linoleic acid oxidation and inhibitory concentration (IC50) were recorded to be in the range of 42.45-96.21% and 14.21-38.18 µg/mL, respectively. Cytotoxicity profile of A. javanica extracts and essential oil was found in the range of 5.82 to 14.47%. In conclusion, A. javanica essential oil could be a potential alternative to chemical additives in the food and pharmaceutical industries.
[Mh] Termos MeSH primário: Amaranthaceae/química
Anti-Infecciosos/farmacologia
Antioxidantes/farmacologia
Citotoxinas/farmacologia
Flavonoides/farmacologia
Óleos Voláteis/farmacologia
[Mh] Termos MeSH secundário: Anti-Infecciosos/isolamento & purificação
Antioxidantes/isolamento & purificação
Compostos de Bifenilo/antagonistas & inibidores
Compostos de Bifenilo/química
Citotoxinas/isolamento & purificação
Flavonoides/isolamento & purificação
Fungos/efeitos dos fármacos
Fungos/crescimento & desenvolvimento
Bactérias Gram-Negativas/efeitos dos fármacos
Bactérias Gram-Negativas/crescimento & desenvolvimento
Bactérias Gram-Positivas/efeitos dos fármacos
Bactérias Gram-Positivas/crescimento & desenvolvimento
Concentração Inibidora 50
Ácido Linoleico/química
Testes de Sensibilidade Microbiana
Óleos Voláteis/isolamento & purificação
Oxirredução
Picratos/antagonistas & inibidores
Picratos/química
Extratos Vegetais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Antioxidants); 0 (Biphenyl Compounds); 0 (Cytotoxins); 0 (Flavonoids); 0 (Oils, Volatile); 0 (Picrates); 0 (Plant Extracts); 9KJL21T0QJ (Linoleic Acid); DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


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[PMID]:28452946
[Au] Autor:Li Y; Zhao Y; Zhou X; Ni W; Dai Z; Yang D; Hao J; Luo L; Liu Y; Luo X; Zhao X
[Ad] Endereço:Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 21 Qingsong Road, Kunming 650203, China. liyuan@mail.kiz.ac.cn.
[Ti] Título:Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair.
[So] Source:Toxins (Basel);9(5), 2017 Apr 28.
[Is] ISSN:2072-6651
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Cytotoxic indole alkaloids from , which belongs to the toxic plant family Apocynaceae, demonstrated impressive antitumor activities in many tumor types, but less application in glioblastoma, which is the lethal brain tumor. In the present study, we reported the anti-glioblastoma activity of an indole alkaloid, 3 -acetonyltabersonine, which was isolated from . 3 -acetonyltabersonine was cytotoxic to glioblastoma cell lines (U87 and T98G) and stem cells at low concentrations. We verified 3 -acetonyltabersonine could suppress tumor cell proliferation and cause apoptosis in glioblastoma stem cells (GSCs). Moreover, detailed investigation of transcriptome study and Western blotting analysis indicated the mitogen activated protein kinase (MAPK) pathway was activated by phosphorylation upon 3 -acetonyltabersonine treatment. Additionally, we found 3 -acetonyltabersonine inhibited DNA damage repair procedures, the accumulated DNA damage stimulated activation of MAPK pathway and, finally, induced apoptosis. Further evidence was consistently obtained from vivo experiments on glioblastoma mouse model: treatment of 3 -acetonyltabersonine could exert pro-apoptotic function and prolong the life span of tumor-bearing mice. These results in vitro and in vivo suggested that 3 -acetonyltabersonine could be a potential candidate antitumor agent.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Citotoxinas/farmacologia
Glioblastoma/genética
Alcaloides de Indol/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Dano ao DNA
Reparo do DNA/efeitos dos fármacos
Glioblastoma/tratamento farmacológico
Seres Humanos
Alcaloides de Indol/uso terapêutico
Masculino
Camundongos Endogâmicos C57BL
Proteínas Quinases Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytotoxins); 0 (Indole Alkaloids); EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28470525
[Au] Autor:Brown JP; Lynch BS; Curry-Chisolm IM; Shafer TJ; Strickland JD
[Ad] Endereço:Integrated Systems Toxicology Division, NHEERL, US EPA, MD105-05, Research Triangle Park, NC, 27711, USA.
[Ti] Título:Assaying Spontaneous Network Activity and Cellular Viability Using Multi-well Microelectrode Arrays.
[So] Source:Methods Mol Biol;1601:153-170, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microelectrode array (MEA) technology is a neurophysiological method that allows for the spontaneous measure of activity in neural cultures and determination of drug and chemical effects thereon. Recent introduction of multi-well MEA (mwMEA) formats have dramatically increased the throughput of this technology, allowing more efficient compound screening. Rapid characterization of compounds for neuroactivity or neurotoxicity hazard evaluation following acute, chronic, or developmental exposures ideally would also consider compound effects on cell health, and to do so in the same well requires a multiplexed approach. Procedures describing the multiplexed method to acute and developmental screening are described in this chapter.
[Mh] Termos MeSH primário: Sobrevivência Celular/efeitos dos fármacos
Citotoxinas/toxicidade
Análise em Microsséries/instrumentação
Microeletrodos
Rede Nervosa/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Testes de Toxicidade/instrumentação
[Mh] Termos MeSH secundário: Animais
Neocórtex/citologia
Cultura Primária de Células
Ratos
Ratos Long-Evans
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytotoxins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6960-9_13


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[PMID]:29337677
[Au] Autor:Mohareb RM; Abdallah AEM; Ahmed EA
[Ad] Endereço:1Department of Chemistry Faculty of Science Cairo University, Giza, A. R. Egypt.
[Ti] Título:Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile.
[So] Source:Acta Pharm;67(4):495-510, 2017 Dec 20.
[Is] ISSN:1846-9558
[Cp] País de publicação:Croatia
[La] Idioma:eng
[Ab] Resumo:Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards thioglycolic acid resulted in thiazole derivative 1. The latter reacted with different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[ 4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized products against six cancer cell lines, namely, human gastric cancer (NUGC), human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7 tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he most active compounds. Their potencies were attributed to the presence of the electron withdrawing groups.
[Mh] Termos MeSH primário: Citotoxinas/farmacologia
Tiazóis/síntese química
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Neoplasias da Mama/tratamento farmacológico
Linhagem Celular Tumoral
Neoplasias do Colo/tratamento farmacológico
Células Hep G2/efeitos dos fármacos
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Nasofaríngeas/tratamento farmacológico
Neoplasias Gástricas/tratamento farmacológico
Tiazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytotoxins); 0 (Thiazoles)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29173760
[Au] Autor:Foy V; Schenk MW; Baker K; Gomes F; Lallo A; Frese KK; Forster M; Dive C; Blackhall F
[Ad] Endereço:Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, UK.
[Ti] Título:Targeting DNA damage in SCLC.
[So] Source:Lung Cancer;114:12-22, 2017 Dec.
[Is] ISSN:1872-8332
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints. Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy. This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease.
[Mh] Termos MeSH primário: Dano ao DNA/genética
Neoplasias Pulmonares/tratamento farmacológico
Rad51 Recombinase/antagonistas & inibidores
Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
[Mh] Termos MeSH secundário: Aurora Quinases/uso terapêutico
Azepinas/uso terapêutico
Benzimidazóis/uso terapêutico
Carbolinas/uso terapêutico
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/genética
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/genética
Citotoxinas/uso terapêutico
Dano ao DNA/efeitos dos fármacos
Reparo do DNA
Etoposídeo/uso terapêutico
Instabilidade Genômica/efeitos dos fármacos
Instabilidade Genômica/genética
Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
Seres Humanos
Neoplasias Pulmonares/genética
Terapia de Alvo Molecular/métodos
Ftalazinas/uso terapêutico
Piperazinas/uso terapêutico
Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
Inibidores de Proteínas Quinases/uso terapêutico
Pirimidinas/uso terapêutico
Rad51 Recombinase/uso terapêutico
Carcinoma de Pequenas Células do Pulmão/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Azepines); 0 (Benzimidazoles); 0 (Carbolines); 0 (Cytotoxins); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (MLN 8237); 0 (PM 01183); 0 (Phthalazines); 0 (Piperazines); 0 (Poly(ADP-ribose) Polymerase Inhibitors); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 01O4K0631N (veliparib); 6PLQ3CP4P3 (Etoposide); 9QHX048FRV (talazoparib); EC 2.7.11.1 (Aurora Kinases); EC 2.7.7.- (Rad51 Recombinase); WOH1JD9AR8 (olaparib)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:29242345
[Au] Autor:Lenarcic T; Albert I; Böhm H; Hodnik V; Pirc K; Zavec AB; Podobnik M; Pahovnik D; Zagar E; Pruitt R; Greimel P; Yamaji-Hasegawa A; Kobayashi T; Zienkiewicz A; Gömann J; Mortimer JC; Fang L; Mamode-Cassim A; Deleu M; Lins L; Oecking C; Feussner I; Mongrand S; Anderluh G; Nürnberger T
[Ad] Endereço:Department for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
[Ti] Título:Eudicot plant-specific sphingolipids determine host selectivity of microbial NLP cytolysins.
[So] Source:Science;358(6369):1431-1434, 2017 12 15.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Necrosis and ethylene-inducing peptide 1-like (NLP) proteins constitute a superfamily of proteins produced by plant pathogenic bacteria, fungi, and oomycetes. Many NLPs are cytotoxins that facilitate microbial infection of eudicot, but not of monocot plants. Here, we report glycosylinositol phosphorylceramide (GIPC) sphingolipids as NLP toxin receptors. Plant mutants with altered GIPC composition were more resistant to NLP toxins. Binding studies and x-ray crystallography showed that NLPs form complexes with terminal monomeric hexose moieties of GIPCs that result in conformational changes within the toxin. Insensitivity to NLP cytolysins of monocot plants may be explained by the length of the GIPC head group and the architecture of the NLP sugar-binding site. We unveil early steps in NLP cytolysin action that determine plant clade-specific toxin selectivity.
[Mh] Termos MeSH primário: Arabidopsis/parasitologia
Citotoxinas/metabolismo
Especificidade de Hospedeiro
Phytophthora/metabolismo
Doenças das Plantas/parasitologia
Pythium/metabolismo
Esfingolipídeos/metabolismo
Toxinas Biológicas/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação
Cristalografia por Raios X
Citotoxinas/química
Etilenos/metabolismo
Esfingolipídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Cytotoxins); 0 (Ethylenes); 0 (Sphingolipids); 0 (Toxins, Biological); 91GW059KN7 (ethylene)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1126/science.aan6874


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[PMID]:28898803
[Au] Autor:Schirinzi GF; Pérez-Pomeda I; Sanchís J; Rossini C; Farré M; Barceló D
[Ad] Endereço:Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona, Catalonia, Spain; Catalan Institute for Water Research (ICRA), Girona, Catalonia, Spain.
[Ti] Título:Cytotoxic effects of commonly used nanomaterials and microplastics on cerebral and epithelial human cells.
[So] Source:Environ Res;159:579-587, 2017 11.
[Is] ISSN:1096-0953
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Plastic wastes are among the major inputs of detritus into aquatic ecosystems. Also, during recent years the increasing use of new materials such as nanomaterials (NMs) in industrial and household applications has contributed to the complexity of waste mixtures in aquatic systems. The current effects and the synergism and antagonisms of mixtures of microplastics (MPLs), NMs and organic compounds on the environment and in human health have, to date, not been well understood but instead they are a cause for general concern. The aim of this work is to contribute to a better understanding of the cytotoxicity of NMs and microplastics/nanoplastics (MPLs/NPLs), at cell level in terms of oxidative stress (evaluating Reactive Oxygen Species effect) and cell viability. Firstly, the individual cytotoxicity of metal nanoparticles (NPs) (AgNPs and AuNPs), of metal oxide NPs (ZrO NPs, CeO NPs, TiO NPs, and Al O NPs), carbon nanomaterials (C fullerene, graphene), and MPLs of polyethylene (PE) and polystyrene (PS) has been evaluated in vitro. Two different cellular lines T98G and HeLa, cerebral and epithelial human cells, respectively, were employed. The cells were exposed during 24-48h to different levels of contaminants, from 10ng/mL to 10µg/mL, under the same conditions. Secondly, the synergistic and antagonistic relationships between fullerenes and other organic contaminants, including an organophosphate insecticide (malathion), a surfactant (sodium dodecylbenzenesulfonate) and a plasticiser (diethyl phthalate) were assessed. The obtained results confirm that oxidative stress is one of the mechanisms of cytotoxicity at cell level, as has been observed for both cell lines and contributes to the current knowledge of the effects of NMs and MPLs-NPLs.
[Mh] Termos MeSH primário: Citotoxinas/toxicidade
Poluentes Ambientais/toxicidade
Nanoestruturas/toxicidade
Estresse Oxidativo/efeitos dos fármacos
Plásticos/toxicidade
[Mh] Termos MeSH secundário: Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Células HeLa
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytotoxins); 0 (Environmental Pollutants); 0 (Plastics)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


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[PMID]:28865279
[Au] Autor:Figueiredo SAC; Salvador JAR; Cortés R; Cascante M
[Ad] Endereço:Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal; Centre for Neuroscience and Cell Biology, Coimbra, Portugal.
[Ti] Título:Design, synthesis and biological evaluation of novel C-29 carbamate celastrol derivatives as potent and selective cytotoxic compounds.
[So] Source:Eur J Med Chem;139:836-848, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Celastrol and its derivatives have been reported for their potent anticancer activity. Among other celastrol analogues, novel carbamate derivatives were designed and synthesised, and their biological activity on the viability of human cancer cell lines was evaluated. Additionally, a preliminary structure-activity relationship study was conducted. Derivative 18 showed the highest activity on cancer cell viability, combined with the best selectivity between malignant cells and non-malignant fibroblasts. Preliminary mechanistic studies of its anti-tumour action indicated that compound 18 has an antiproliferative effect on SKOV-3 human ovarian cancer cells (IC = 0.54 µM). The results also suggested that its potent anticancer activity is mediated by apoptosis, and that this process was mainly the result of the activation of the extrinsic apoptotic pathway. Moreover, our results demonstrated the potential of derivative 18 as a new agent for combinatorial drug therapy for ovarian cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Citotoxinas/farmacologia
Desenho de Drogas
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Citotoxinas/síntese química
Citotoxinas/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Triterpenos/síntese química
Triterpenos/química
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytotoxins); 0 (Triterpenes); L8GG98663L (tripterine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE


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[PMID]:28818768
[Au] Autor:Poornima B; Siva B; Venkanna A; Shankaraiah G; Jain N; Yadav DK; Misra S; Babu KS
[Ad] Endereço:Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
[Ti] Título:Novel Gomisin B analogues as potential cytotoxic agents: Design, synthesis, biological evaluation and docking studies.
[So] Source:Eur J Med Chem;139:441-453, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:As part of pharmacological-phytochemical integrated studies on medicinal flora, Gomisin B (1) was isolated as major phytochemical lead from schisandra grandiflora, a plant traditionally used in different Asian systems of medicine. A series of 1,2,3-triazoles derivatives were synthesized at the C-7' position of the gomisin B core through diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5q) were well characterized using modern spectroscopic techniques and evaluated for their anti-cancer activity against a panel of five human cancerous cell-lines. Among them, compound 5b exhibited the best cytotoxicity against SIHA cell (IC 0.24 µM) which was more than the standard drug doxorubicin, while the other derivatives were exhibited moderate to low activities in tested cell lines. The cell cycle analysis indicated that compound 5b stalled HeLa cells at G2/M phase. 5b promoted tubulin polymerization and this was supported by the docking studies, wherein 5b showed significant binding affinity at the colchicine binding pocket of tubulin. Overall, we identified a novel small molecule that demonstrated anticancer activity by promoting in vitro tubulin assembly.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Citotoxinas/farmacologia
Dioxóis/farmacologia
Desenho de Drogas
Lignanas/farmacologia
Simulação de Acoplamento Molecular
Compostos Policíclicos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Ciclo-Octanos/síntese química
Ciclo-Octanos/química
Ciclo-Octanos/farmacologia
Citotoxinas/síntese química
Citotoxinas/química
Dioxóis/síntese química
Dioxóis/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Lignanas/síntese química
Lignanas/química
Estrutura Molecular
Compostos Policíclicos/síntese química
Compostos Policíclicos/química
Schisandra/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cyclooctanes); 0 (Cytotoxins); 0 (Dioxoles); 0 (Lignans); 0 (Polycyclic Compounds); 58546-55-7 (schisantherin B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE



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