Base de dados : MEDLINE
Pesquisa : D02.092.384 [Categoria DeCS]
Referências encontradas : 1036 [refinar]
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[PMID]:28783875
[Au] Autor:Horwath MC; Bell-Horwath TR; Lescano V; Krishnan K; Merino EJ; Deepe GS
[Ad] Endereço:Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, 333 Burnet Avenue, Cincinnati, OH, 45229, USA.
[Ti] Título:Antifungal Activity of the Lipophilic Antioxidant Ferrostatin-1.
[So] Source:Chembiochem;18(20):2069-2078, 2017 Oct 18.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Ferrostatin-1 (Fer-1) is a lipophilic antioxidant that effectively blocks ferroptosis, a distinct non-apoptotic form of cell death caused by lipid peroxidation. During many infections, both pathogens and host cells are subjected to oxidative stress, but the occurrence of ferroptosis had not been investigated. We examined ferroptosis in macrophages infected with the pathogenic yeast Histoplasma capsulatum. Unexpectedly, Fer-1 not only reduced the death of macrophages infected in vitro, but inhibited the growth of H. capsulatum and related species Paracoccidioides lutzii and Blastomyces dermatitidis at concentrations under 10 µm. Other antioxidant ferroptosis inhibitors, including liproxstatin-1, did not prevent fungal growth or reduce macrophage death. Structural analysis revealed a potential similarity of Fer-1 to inhibitors of fungal sterol synthesis, and ergosterol content of H. capsulatum decreased more than twofold after incubation with Fer-1. Strikingly, additional Fer-1 analogues with slight differences from Fer-1 had limited impact on fungal growth. In conclusion, the ferroptosis inhibitor Fer-1 has unexpected antifungal potency distinct from its antiferroptotic activity.
[Mh] Termos MeSH primário: Antifúngicos/química
Antifúngicos/farmacologia
Antioxidantes/química
Antioxidantes/farmacologia
Cicloexilaminas/química
Cicloexilaminas/farmacologia
Interações Hidrofóbicas e Hidrofílicas
Fenilenodiaminas/química
Fenilenodiaminas/farmacologia
[Mh] Termos MeSH secundário: Histoplasma/efeitos dos fármacos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Antioxidants); 0 (Cyclohexylamines); 0 (Phenylenediamines); 0 (ferrostatin-1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700105


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[PMID]:28595877
[Au] Autor:Probst L; Dächert J; Schenk B; Fulda S
[Ad] Endereço:Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany.
[Ti] Título:Lipoxygenase inhibitors protect acute lymphoblastic leukemia cells from ferroptotic cell death.
[So] Source:Biochem Pharmacol;140:41-52, 2017 Sep 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ferroptosis has recently been identified as a mode of programmed cell death. However, little is yet known about the signaling mechanism. Here, we report that lipoxygenases (LOX) contribute to the regulation of RSL3-induced ferroptosis in acute lymphoblastic leukemia (ALL) cells. We show that the glutathione (GSH) peroxidase 4 (GPX4) inhibitor RSL3 triggers lipid peroxidation, production of reactive oxygen species (ROS) and cell death in ALL cells. All these events are impeded in the presence of Ferrostatin-1 (Fer-1), a small-molecule inhibitor of lipid peroxidation. Also, lipid peroxidation and ROS production precede the induction of cell death, underscoring their contribution to cell death upon exposure to RSL3. Importantly, LOX inhibitors, including the selective 12/15-LOX inhibitor Baicalein and the pan-LOX inhibitor nordihydroguaiaretic acid (NDGA), protect ALL cells from RSL3-stimulated lipid peroxidation, ROS generation and cell death, indicating that LOX contribute to ferroptosis. RSL3 triggers lipid peroxidation and cell death also in FAS-associated Death Domain (FADD)-deficient cells which are resistant to death receptor-induced apoptosis indicating that the induction of ferroptosis may bypass apoptosis resistance. By providing new insights into the molecular regulation of ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in ALL.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carbolinas/farmacologia
Glutationa Peroxidase/antagonistas & inibidores
Peroxidação de Lipídeos/efeitos dos fármacos
Inibidores de Lipoxigenase/farmacologia
Estresse Oxidativo/efeitos dos fármacos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Antineoplásicos/química
Antioxidantes/farmacologia
Araquidonato 12-Lipoxigenase/química
Araquidonato 12-Lipoxigenase/genética
Araquidonato 12-Lipoxigenase/metabolismo
Araquidonato 15-Lipoxigenase/química
Araquidonato 15-Lipoxigenase/genética
Araquidonato 15-Lipoxigenase/metabolismo
Carbolinas/antagonistas & inibidores
Morte Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Cicloexilaminas/farmacologia
Proteína de Domínio de Morte Associada a Fas/genética
Proteína de Domínio de Morte Associada a Fas/metabolismo
Flavanonas/farmacologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Glutationa Peroxidase/genética
Glutationa Peroxidase/metabolismo
Seres Humanos
Cinética
Masoprocol/farmacologia
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Fenilenodiaminas/farmacologia
Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia
Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
Espécies Reativas de Oxigênio/antagonistas & inibidores
Espécies Reativas de Oxigênio/metabolismo
alfa-Tocoferol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antioxidants); 0 (Carbolines); 0 (Cyclohexylamines); 0 (FADD protein, human); 0 (Fas-Associated Death Domain Protein); 0 (Flavanones); 0 (Lipoxygenase Inhibitors); 0 (Neoplasm Proteins); 0 (Phenylenediamines); 0 (RSL3 compound); 0 (Reactive Oxygen Species); 0 (ferrostatin-1); 49QAH60606 (baicalein); 7BO8G1BYQU (Masoprocol); EC 1.11.1.12 (phospholipid-hydroperoxide glutathione peroxidase); EC 1.11.1.9 (Glutathione Peroxidase); EC 1.13.11.31 (Arachidonate 12-Lipoxygenase); EC 1.13.11.31. (ALOX12 protein, human); EC 1.13.11.33 (ALOX15 protein, human); EC 1.13.11.33 (Arachidonate 15-Lipoxygenase); H4N855PNZ1 (alpha-Tocopherol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE


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[PMID]:28544967
[Au] Autor:Ishihara K; Watanabe R; Uchida H; Suzuki T; Yamashita M; Takenaka H; Nazifi E; Matsugo S; Yamaba M; Sakamoto T
[Ad] Endereço:Marine Biochemistry Division, National Research Institute of Fisheries Science, Yokohama 236-8648, Japan. Electronic address: hplc@affrc.go.jp.
[Ti] Título:Novel glycosylated mycosporine-like amino acid, 13-O-(ß-galactosyl)-porphyra-334, from the edible cyanobacterium Nostoc sphaericum-protective activity on human keratinocytes from UV light.
[So] Source:J Photochem Photobiol B;172:102-108, 2017 Jul.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A UV-absorbing compound was purified and identified as a novel glycosylated mycosporine-like amino acid (MAA), 13-O-ß-galactosyl-porphyra-334 (ß-Gal-P334) from the edible cyanobacterium Nostoc sphaericum, known as "ge xian mi" in China and "cushuro" in Peru. Occurrence of the hexosylated derivative of shinorine (hexosyl-shinorine) was also supported by LC-MS/MS analysis. ß-Gal-P334 accounted for about 86.5% of total MAA in N. sphaericum, followed by hexosyl-shinorine (13.2%) and porphyra-334 (0.2%). ß-Gal-P334 had an absorption maximum at 334nm and molecular absorption coefficient was 46,700 at 334nm. Protection activity of ß-Gal-P334 from UVB and UVA+8-methoxypsoralen induced cell damage on human keratinocytes (HaCaT) was assayed in comparison with other MAA (porphyra-334, shinorine, palythine and mycosporine-glycine). The UVB protection activity was highest in mycosporine-glycine, followed by palythine, ß-Gal-P334, porphyra-334 and shinorine in order. ß-Gal-P334 had highest protection activity from UVA+8-methoxypsoralen induced cell damage followed by porphyra-334, shinorine, mycosporine-glycine and palythine. We also found an antioxidant (radical-scavenging) activity of ß-Gal-P334 by colorimetric and ESR methods. From these findings, ß-Gal-P334 was suggested to play important roles in stress tolerant mechanisms such as UV and oxidative stress in N. sphaericum as a major MAA. We also consider that the newly identified MAA, ß-Gal-P334 has a potential for use as an ingredient of cosmetics and toiletries.
[Mh] Termos MeSH primário: Cicloexanonas/química
Glicina/análogos & derivados
Nostoc/química
Estresse Oxidativo/efeitos dos fármacos
Substâncias Protetoras/farmacologia
Raios Ultravioleta
[Mh] Termos MeSH secundário: Aminoácidos/química
Antioxidantes/química
Antioxidantes/isolamento & purificação
Antioxidantes/farmacologia
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos da radiação
Cromatografia Líquida de Alta Pressão
Cicloexanonas/isolamento & purificação
Cicloexanonas/farmacologia
Cicloexilaminas/química
Glicina/química
Glicina/isolamento & purificação
Glicina/farmacologia
Glicosilação
Seres Humanos
Queratinócitos/citologia
Queratinócitos/efeitos dos fármacos
Queratinócitos/efeitos da radiação
Conformação Molecular
Nostoc/metabolismo
Estresse Oxidativo/efeitos da radiação
Substâncias Protetoras/química
Substâncias Protetoras/isolamento & purificação
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Antioxidants); 0 (Cyclohexanones); 0 (Cyclohexylamines); 0 (Protective Agents); 0 (porphyra-334); 0 (shinorine); TE7660XO1C (Glycine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE


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[PMID]:28385507
[Au] Autor:Li H; Zhou T; Liu H; Xu F; Niu Y; Wang C; Liang L; Xu P
[Ad] Endereço:Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
[Ti] Título:Discovery of a cobalt complex with high MEK1 binding affinity.
[So] Source:Bioorg Med Chem Lett;27(10):2221-2224, 2017 05 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of Schiff base ligands (L -L ) and their cobalt(II) complexes (1-5) were designed and synthesized for MEK1 binding experiment. The biological evaluation results showed that Bis(N,N'-disalicylidene)-3,4-phenylenediamine-cobalt(II) 1 and Bis(N,N'-disalicylidene)-1,2-cyclohexanediamine-cobalt(II) 2 are much more effective than the parent Schiff bases (L and L ). Importantly, 2 exhibited MEK1 binding affinity with IC 71nM, which is so far the best result for metal complexes and more potent than U0126 (7.02µM) and AZD6244 (2.20µM). Docking study was used to elucidate the binding modes of complex 2 with MEK1. Thus cobalt(II) complex 2 may be further developed as a novel MEK1 inhibitor.
[Mh] Termos MeSH primário: Cobalto/química
Complexos de Coordenação/química
MAP Quinase Quinase 1/metabolismo
Inibidores de Proteínas Quinases/química
[Mh] Termos MeSH secundário: Sítios de Ligação
Complexos de Coordenação/síntese química
Complexos de Coordenação/metabolismo
Cicloexilaminas/química
Avaliação Pré-Clínica de Medicamentos
Concentração Inibidora 50
MAP Quinase Quinase 1/antagonistas & inibidores
Simulação de Acoplamento Molecular
Ligação Proteica
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/metabolismo
Estrutura Terciária de Proteína
Bases de Schiff/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Cyclohexylamines); 0 (Protein Kinase Inhibitors); 0 (Schiff Bases); 3G0H8C9362 (Cobalt); C82TX76BHH (1,2-cyclohexanediamine); EC 2.7.12.2 (MAP Kinase Kinase 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE


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[PMID]:28334805
[Au] Autor:Salomone A; Palamar JJ; Gerace E; Di Corcia D; Vincenti M
[Ad] Endereço:Centro Regionale Antidoping e di Tossicologia "A. Bertinaria", Orbassano, Turin, Italy.
[Ti] Título:Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population.
[So] Source:J Anal Toxicol;41(5):376-381, 2017 Jun 01.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography-tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance-either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS-the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use.
[Mh] Termos MeSH primário: Cabelo/química
Psicotrópicos/análise
Drogas Ilícitas/análise
Detecção do Abuso de Substâncias/métodos
[Mh] Termos MeSH secundário: Cicloexanonas/análise
Cicloexilaminas/análise
Seres Humanos
Metanfetamina/análogos & derivados
Metanfetamina/análise
N-Metil-3,4-Metilenodioxianfetamina/análise
Pentanonas/análise
Prevalência
Pirrolidinas/análise
Transtornos Relacionados ao Uso de Substâncias/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-phenyl-2-(1-pyrrolidinyl)-1-pentanone); 0 (Cyclohexanones); 0 (Cyclohexylamines); 0 (Pentanones); 0 (Psychotropic Drugs); 0 (Pyrrolidines); 0 (Street Drugs); 44RAL3456C (Methamphetamine); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine); L4I4B1R01F (methylone); ZO5ZCE6E12 (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bkx020


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[PMID]:28281333
[Au] Autor:Belyanskaya SL; Ding Y; Callahan JF; Lazaar AL; Israel DI
[Ad] Endereço:GlaxoSmithKline R&D, 830 Winter Street, Waltham, MA, 02451, USA.
[Ti] Título:Discovering Drugs with DNA-Encoded Library Technology: From Concept to Clinic with an Inhibitor of Soluble Epoxide Hydrolase.
[So] Source:Chembiochem;18(9):837-842, 2017 May 04.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs.
[Mh] Termos MeSH primário: DNA/química
Epóxido Hidrolases/antagonistas & inibidores
Bibliotecas de Moléculas Pequenas/química
[Mh] Termos MeSH secundário: Ensaios Clínicos como Assunto
Técnicas de Química Combinatória
Cicloexilaminas/química
Cicloexilaminas/farmacocinética
DNA/metabolismo
Descoberta de Drogas
Epóxido Hidrolases/genética
Epóxido Hidrolases/metabolismo
Células HEK293
Meia-Vida
Seres Humanos
Ligantes
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Triazinas/química
Triazinas/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclohexylamines); 0 (Ligands); 0 (N-((4-cyano-2-(trifluoromethyl)phenyl)methyl)-3-((4-methyl-6-(methylamino)-1,3,5-triazin-2-yl)amino)cyclohexanecarboxamide); 0 (Recombinant Proteins); 0 (Small Molecule Libraries); 0 (Triazines); 9007-49-2 (DNA); EC 3.3.2.- (Epoxide Hydrolases); EC 3.3.2.10 (EPHX2 protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170607
[Lr] Data última revisão:
170607
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700014


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[PMID]:28213175
[Au] Autor:Hartmann A; Murauer A; Ganzera M
[Ad] Endereço:Institute of Pharmacy, Pharmacognosy, University of Innsbruck, 6020 Innsbruck, Austria.
[Ti] Título:Quantitative analysis of mycosporine-like amino acids in marine algae by capillary electrophoresis with diode-array detection.
[So] Source:J Pharm Biomed Anal;138:153-157, 2017 May 10.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Marine species have evolved a variety of physical or chemical strategies to diminish damage from elevated environmental ultraviolet radiation. Mycosporine-like amino acids, a group of widely distributed small water soluble compounds, are biologically relevant because of their photo-protective potential. In addition, presumed antioxidant and skin protective strategies raise the interest for possible medicinal and cosmetic applications. In this study the first CE method for the quantification of mycosporine-like amino acids in marine species is presented. A borate buffer system consisting of 30mM sodium tetraborate in water at a pH-value of 10.3 enabled the baseline separation of five MAAs, namely palythine, mycosporine-serinol, asterina-330, shinorine and porphyra-334, in 27min. Separation voltage, temperature and detection wavelength were 25kV, 25°C and 320nm, respectively. The optimized method was fully validated and applied for the quantitative determination of MAAs in the marine macroalgae Palmaria palmata, Porphyra umbilicalis, and Porphyra sp., as well as the lichen Lichina pygmaea.
[Mh] Termos MeSH primário: Aminoácidos/química
Cicloexanonas/química
Propilenoglicóis/química
Rodófitas/química
Alga Marinha/química
[Mh] Termos MeSH secundário: Antioxidantes/química
Organismos Aquáticos
Cicloexanóis/química
Cicloexilaminas/química
Eletroforese Capilar/métodos
Glicina/análogos & derivados
Glicina/química
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Antioxidants); 0 (Cyclohexanols); 0 (Cyclohexanones); 0 (Cyclohexylamines); 0 (Propylene Glycols); 0 (asterina-330); 0 (mycosporine-serinol); 0 (palythine); 0 (porphyra-334); 0 (shinorine); TE7660XO1C (Glycine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170219
[St] Status:MEDLINE


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[PMID]:28206707
[Au] Autor:Harper BW; Friedman-Ezra A; Sirota R; Petruzzella E; Aldrich-Wright JR; Gibson D
[Ad] Endereço:Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
[Ti] Título:Probing the Interactions of Cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and Its Pt Derivatives with Human Serum.
[So] Source:ChemMedChem;12(7):510-519, 2017 Apr 06.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The discrepancy between the in vitro cytotoxic results and the in vivo performance of Pt56MeSS prompted us to look into its interactions and those of its Pt derivatives with human serum (HS), human serum albumin (HSA), lipoproteins, and serum-supplemented cell culture media. The Pt complex, Pt56MeSS, binds noncovalently and reversibly to slow-tumbling proteins in HS and in cell culture media and interacts through the phenanthroline group with HSA, with a K value of ∼1.5×10 m. All Pt complexes were found to be stable toward reduction in HS, but those with axial carboxylate ligands, cct-[Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenantroline)(acetato) ](TFA) (Pt56MeSS(OAc) ) and cct-[Pt(1S,2S-DACH)(5,6-dimehtyl-1,10-phenantroline)(phenylbutyrato) ](TFA) (Pt56MeSS(PhB) ), were spontaneously reduced at pH 7 or higher in phosphate buffer, but not in Tris buffer (pH 8). HS also decreased the rate of reduction by ascorbate of the Pt complexes relative to the reduction rates in phosphate buffer, suggesting that for this compound class, phosphate buffer is not a good model for HS.
[Mh] Termos MeSH primário: Complexos de Coordenação/química
Platina/química
[Mh] Termos MeSH secundário: Ácido Ascórbico/química
Complexos de Coordenação/sangue
Complexos de Coordenação/síntese química
Cicloexilaminas/química
Estabilidade de Medicamentos
Técnicas Eletroquímicas
Seres Humanos
Espectroscopia de Ressonância Magnética
Oxirredução
Fenantrolinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Cyclohexylamines); 0 (Phenanthrolines); 49DFR088MY (Platinum); C82TX76BHH (1,2-cyclohexanediamine); PQ6CK8PD0R (Ascorbic Acid); W4X6ZO7939 (1,10-phenanthroline)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700092


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[PMID]:28204974
[Au] Autor:Imai H; Matsuoka M; Kumagai T; Sakamoto T; Koumura T
[Ad] Endereço:Department of Hygienic Chemistry, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. imaih@pharm.kitasato-u.ac.jp.
[Ti] Título:Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis.
[So] Source:Curr Top Microbiol Immunol;403:143-170, 2017.
[Is] ISSN:0070-217X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Glutathione peroxidase 4 (Phospholipid hydroperoxide glutathione peroxidase, PHGPx) can directly reduce phospholipid hydroperoxide. Depletion of GPx4 induces lipid peroxidation-dependent cell death in embryo, testis, brain, liver, heart, and photoreceptor cells of mice. Administration of vitamin E in tissue specific GPx4 KO mice restored tissue damage in testis, liver, and heart. These results indicate that suppression of phospholipid peroxidation is essential for cell survival in normal tissues in mice. Ferroptosis is an iron-dependent non-apoptotic cell death that can elicited by pharmacological inhibiting the cystine/glutamate antiporter, system Xc (type I) or directly binding and loss of activity of GPx4 (Type II) in cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression, but not in normal cells. Ferroptosis by Erastin (Type I) and RSL3 (RAS-selective lethal 3, Type II) treatment was suppressed by an iron chelator, vitamin E and Ferrostatin-1, antioxidant compound. GPx4 can regulate ferroptosis by suppression of phospholipid peroxidation in erastin and RSL3-induced ferroptosis. Recent works have identified several regulatory factors of erastin and RSL3-induced ferroptosis. In our established GPx4-deficient MEF cells, depletion of GPx4 induce iron and 15LOX-independent lipid peroxidation at 26 h and caspase-independent cell death at 72 h, whereas erastin and RSL3 treatment resulted in iron-dependent ferroptosis by 12 h. These results indicated the possibility that the mechanism of GPx4-depleted cell death might be different from that of ferroptosis induced by erastin and RSL3.
[Mh] Termos MeSH primário: Morte Celular/fisiologia
Cicloexilaminas/metabolismo
Glutationa Peroxidase/metabolismo
Ferro/metabolismo
Peroxidação de Lipídeos/fisiologia
Fenilenodiaminas/metabolismo
[Mh] Termos MeSH secundário: Animais
Carbolinas/farmacologia
Caspases/metabolismo
Seres Humanos
Piperazinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Carbolines); 0 (Cyclohexylamines); 0 (Phenylenediamines); 0 (Piperazines); 0 (RSL3 compound); 0 (erastin); 0 (ferrostatin-1); E1UOL152H7 (Iron); EC 1.11.1.12 (phospholipid-hydroperoxide glutathione peroxidase); EC 1.11.1.9 (Glutathione Peroxidase); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1007/82_2016_508


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[PMID]:28176540
[Au] Autor:Morales F; Ramírez A; Morata-Tarifa C; Navarro SA; Marchal JA; Campos JM; Conejo-García A
[Ad] Endereço:Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Granada 18071, Spain.
[Ti] Título:Antitumoral activity of 1,2-diaminocyclohexane derivatives in breast, colon and skin human cancer cells.
[So] Source:Future Med Chem;9(3):293-302, 2017 Mar.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: Cancer is among the leading causes of death worldwide. Medical interest has focused on macrocyclic polyamines because of their properties as antitumor agents. Results/Methodology: We have designed and synthesized a series of 1,2-diaminocyclohexane derivatives with notable in vitro antiproliferative activities against the MCF-7, HCT-116 and A375 cancer cell lines. Cell cycle and apoptosis analyses were also carried out. Our results show that all the compounds are potent cytotoxic agents, especially against the A375 cell line. CONCLUSION: The selective activity of the macrocyclic derivative against A375, via apoptosis, supposes a great advantage for future therapeutic use. This exemplifies the potential of 1,2-diaminocyclohexane derivatives to qualify as lead structures for future anticancer drug development due to their easy syntheses and noteworthy bioactivity.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Cicloexilaminas/síntese química
Cicloexilaminas/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/química
Antineoplásicos/uso terapêutico
Apoptose
Neoplasias da Mama
Ciclo Celular
Linhagem Celular Tumoral
Neoplasias do Colo
Cicloexilaminas/uso terapêutico
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Seres Humanos
Concentração Inibidora 50
Neoplasias Cutâneas
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cyclohexylamines); C82TX76BHH (1,2-cyclohexanediamine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2016-0212



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