Base de dados : MEDLINE
Pesquisa : D02.806.400.249 [Categoria DeCS]
Referências encontradas : 6941 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 695 ir para página                         

  1 / 6941 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27082015
[Au] Autor:Bose A; Surugihalli C; Pande P; Champeil E; Basu AK
[Ad] Endereço:Department of Chemistry, University of Connecticut , Storrs, Connecticut 06269, United States.
[Ti] Título:Comparative Error-Free and Error-Prone Translesion Synthesis of N(2)-2'-Deoxyguanosine Adducts Formed by Mitomycin C and Its Metabolite, 2,7-Diaminomitosene, in Human Cells.
[So] Source:Chem Res Toxicol;29(5):933-9, 2016 05 16.
[Is] ISSN:1520-5010
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N(2) adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N(2)-MC and dG-N(2)-2,7-DAM were 38 ± 3 and 27 ± 3%, respectively, compared to that of a control plasmid. This indicates that both adducts block DNA synthesis and that dG-N(2)-2,7-DAM is a stronger replication block than dG-N(2)-MC. TLS of each adducted construct was reduced upon siRNA knockdown of pol η, pol κ, or pol ζ. For both adducts, the most significant reduction occurred with knockdown of pol κ, which suggests that pol κ plays a major role in TLS of these dG-N(2) adducts. Analysis of the progeny showed that both adducts were mutagenic, and the mutation frequencies (MF) of dG-N(2)-MC and dG-N(2)-2,7-DAM were 18 ± 3 and 10 ± 1%, respectively. For both adducts, the major type of mutation was G → T transversions. Knockdown of pol η and pol ζ reduced the MF of dG-N(2)-MC and dG-N(2)-2,7-DAM, whereas knockdown of pol κ increased the MF of these adducts. This suggests that pol κ predominantly carries out error-free TLS, whereas pol η and pol ζ are involved in error-prone TLS. The largest reduction in MF by 78 and 80%, respectively, for dG-N(2)-MC and dG-N(2)-2,7-DAM constructs occurred when pol η, pol ζ, and Rev1 were simultaneously knocked down. This result strongly suggests that, unlike pol κ, these three TLS polymerases cooperatively perform the error-prone TLS of these adducts.
[Mh] Termos MeSH primário: Desoxiguanosina/química
Mitomicina/química
Mitomicinas/química
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Mitomycins); 50SG953SK6 (Mitomycin); 78598-43-3 (2,7-diaminomitosene); G9481N71RO (Deoxyguanosine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170415
[Lr] Data última revisão:
170415
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160416
[St] Status:MEDLINE
[do] DOI:10.1021/acs.chemrestox.6b00087


  2 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26894558
[Au] Autor:Champeil E; Cheng SY; Huang BT; Conchero-Guisan M; Martinez T; Paz MM; Sapse AM
[Ad] Endereço:John Jay College of Criminal Justice, New York, 524 West 59th Street, New York, NY 10019, USA; The Graduate Center of the City University of New York, New York, NY 10016, USA. Electronic address: echampeil@jjay.cuny.edu.
[Ti] Título:Synthesis of Mitomycin C and Decarbamoylmitomycin C N(2) deoxyguanosine-adducts.
[So] Source:Bioorg Chem;65:90-9, 2016 Apr.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitomycin C (MC) and Decarbamoylmitomycin C (DMC) - a derivative of MC lacking the carbamate on C10 - are DNA alkylating agents. Their cytotoxicity is attributed to their ability to generate DNA monoadducts as well as intrastrand and interstrand cross-links (ICLs). The major monoadducts generated by MC and DMC in tumor cells have opposite stereochemistry at carbon one of the guanine-mitosene bond: trans (or alpha) for MC and cis (or beta) for DMC. We hypothesize that local disruptions of DNA structure from trans or cis adducts are responsible for the different biochemical responses produced by MC and DMC. Access to DNA substrates bearing cis and trans MC/DMC lesions is essential to verify this hypothesis. Synthetic oligonucleotides bearing trans lesions can be obtained by bio-mimetic methods. However, this approach does not yield cis adducts. This report presents the first chemical synthesis of a cis mitosene DNA adduct. We also examined the stereopreference exhibited by the two drugs at the mononucleotide level by analyzing the formation of cis and trans adducts in the reaction of deoxyguanosine with MC or DMC using a variety of activation conditions. In addition, we performed Density Functional Theory calculations to evaluate the energies of these reactions. Direct alkylation under autocatalytic or bifunctional conditions yielded preferentially alpha adducts with both MC and DMC. DFT calculations showed that under bifunctional activation, the thermodynamically favored adducts are alpha, trans, for MC and beta, cis, for DMC. This suggests that the duplex DNA structure may stabilize/oriente the activated pro-drugs so that, with DMC, formation of the thermodynamically favored beta products are possible in a cellular environment.
[Mh] Termos MeSH primário: Adutos de DNA/síntese química
Desoxiguanosina/síntese química
Mitomicina/síntese química
Mitomicinas/síntese química
[Mh] Termos MeSH secundário: Adutos de DNA/química
Desoxiguanosina/química
Mitomicina/química
Mitomicinas/química
Conformação Molecular
Teoria Quântica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Adducts); 0 (Mitomycins); 26909-37-5 (10-decarbamoylmitomycin C); 50SG953SK6 (Mitomycin); G9481N71RO (Deoxyguanosine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160220
[St] Status:MEDLINE


  3 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26541587
[Au] Autor:Mallory CM; Carfi RP; Moon S; Cornell KA; Warner DL
[Ad] Endereço:Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA. Electronic address: chrismmallory@gmail.com.
[Ti] Título:Modification of cellular DNA by synthetic aziridinomitosenes.
[So] Source:Bioorg Med Chem;23(23):7378-85, 2015 Dec 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two synthetic aziridinomitosenes (AZMs), Me-AZM and H-AZM, structurally related to mitomycin C (MC) were evaluated for their anticancer activity against six cancer cell lines (HeLa, Jurkat, T47D, HepG2, HL-60, and HuT-78) and tested for their DNA-modifying abilities in Jurkat cells. Cytotoxicity assays showed that Me-AZM is up to 72-fold and 520-fold more potent than MC and H-AZM, respectively. Me-AZM also demonstrated increased DNA modification over MC and H-AZM in alkaline COMET and Hoechst fluorescence assays that measured crosslinks in cellular DNA. Me-AZM and H-AZM treatment of Jurkat cells was found to sponsor significant DNA-protein crosslinks using a K-SDS assay. The results clearly indicate that the AZM C6/C7 substitution pattern plays an important role in drug activity and supports both DNA-DNA and DNA-protein adduct formation as mechanisms for inducing cytotoxic effects.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Reagentes para Ligações Cruzadas/farmacologia
DNA/metabolismo
Mitomicinas/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Reagentes para Ligações Cruzadas/química
Adutos de DNA/metabolismo
Seres Humanos
Mitomicinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cross-Linking Reagents); 0 (DNA Adducts); 0 (Mitomycins); 9007-49-2 (DNA)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161201
[Lr] Data última revisão:
161201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151107
[St] Status:MEDLINE


  4 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25565400
[Au] Autor:Xiao G; Kue P; Bhosle R; Bargonetti J
[Ad] Endereço:a Department of Biological Sciences; Hunter College and The Graduate Center Biology Program ; City University of New York ; New York , NY USA.
[Ti] Título:Decarbamoyl mitomycin C (DMC) activates p53-independent ataxia telangiectasia and rad3 related protein (ATR) chromatin eviction.
[So] Source:Cell Cycle;14(5):744-54, 2015.
[Is] ISSN:1551-4005
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interstrand crosslinks induce DNA replication fork stalling that in turn activates the ATR-dependent checkpoint and DNA repair on nuclear chromatin. Mitomycin C (MC) and Decarbamoyl Mitomycin C (DMC) induce different types of DNA crosslinks with DMC being a more cytotoxic agent. We previously reported that the novel DMC induced ß-interstrand DNA crosslinks induce a p53-independent form of cell death. The p53-independent DMC cytotoxicity associates with the activation, and subsequent depletion, of Chk1. In this study we further dissect the novel DMC signal transduction pathway and asked how it influences chromatin-associated proteins. We found that treatment with DMC, but not MC, stimulated the disassociation of ATR from chromatin and re-localization of ATR to the cytoplasm. The chromatin eviction of ATR was coupled with the formation of nuclear Rad51 foci and the phosphorylation of Chk1. Furthermore, DMC but not MC, activated expression of gadd45α mRNA. Importantly, knocking down p53 via shRNA did not inhibit the DMC-induced disassociation of ATR from chromatin or reduce the activation of transcription of gadd45α. Our results suggest that DMC induces a p53-independent disassociation of ATR from chromatin that facilitates Chk1 checkpoint activation and Rad51 chromatin recruitment. Our findings provide evidence that ATR chromatin eviction in breast cancer cells is an area of study that should be focused on for inducing p53-independent cell death.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Mitomicinas/farmacologia
Proteína Supressora de Tumor p53/metabolismo
[Mh] Termos MeSH secundário: Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Proteínas de Ciclo Celular/metabolismo
Morte Celular/efeitos dos fármacos
Quinase do Ponto de Checagem 1
DNA/metabolismo
Dano ao DNA
Recombinação Homóloga/efeitos dos fármacos
Seres Humanos
Células MCF-7
Modelos Biológicos
Proteínas Nucleares/metabolismo
Fosforilação/efeitos dos fármacos
Fosfosserina/metabolismo
Ligação Proteica/efeitos dos fármacos
Proteínas Quinases/metabolismo
Rad51 Recombinase/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Chromatin); 0 (GADD45A protein, human); 0 (Mitomycins); 0 (Nuclear Proteins); 0 (Tumor Suppressor Protein p53); 17885-08-4 (Phosphoserine); 26909-37-5 (10-decarbamoylmitomycin C); 9007-49-2 (DNA); EC 2.7.- (Protein Kinases); EC 2.7.11.1 (ATR protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.1 (CHEK1 protein, human); EC 2.7.11.1 (Checkpoint Kinase 1); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 2.7.7.- (Rad51 Recombinase)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150108
[St] Status:MEDLINE
[do] DOI:10.1080/15384101.2014.997517


  5 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25044229
[Au] Autor:Zheng Z; Touve M; Barnes J; Reich N; Zhang L
[Ad] Endereço:Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA (USA) http://www.chem.ucsb.edu/∼zhang/index.html.
[Ti] Título:Synthesis-enabled probing of mitosene structural space leads to improved IC50 over mitomycin C.
[So] Source:Angew Chem Int Ed Engl;53(35):9302-5, 2014 Aug 25.
[Is] ISSN:1521-3773
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A DNA crosslinking approach, which is distinct but related to the double alkylation by mitomycin C, involving a novel electrophilic spiro-cyclopropane intermediate is hypothesized. Rational design and substantial structural simplification permitted the expedient chemical synthesis and rapid discovery of MTSB-6, a mitomycin C analogue which is twice as potent as mitomycin C against the prostate cancer cells. MTSB-6 shows improvements in its selective action against noncancer prostate cells over mitomycin C. This hypothesis-driven discovery opens novel yet synthetically accessible mitosene structural space for discovering more potent and less toxic therapeutic candidates.
[Mh] Termos MeSH primário: Mitomicina/farmacologia
Mitomicinas/química
Mitomicinas/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Concentração Inibidora 50
Mitomicina/química
Mitomicinas/síntese química
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Mitomycins); 3567-35-9 (mitosene); 50SG953SK6 (Mitomycin)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:161025
[Lr] Data última revisão:
161025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140722
[St] Status:MEDLINE
[do] DOI:10.1002/anie.201402268


  6 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24909504
[Au] Autor:Eikesdal HP; Knappskog S; Aas T; Lønning PE
[Ad] Endereço:Section of Oncology, Department of Clinical Science, University of Bergen , Bergen , Norway.
[Ti] Título:TP53 status predicts long-term survival in locally advanced breast cancer after primary chemotherapy.
[So] Source:Acta Oncol;53(10):1347-55, 2014 Oct.
[Is] ISSN:1651-226X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Before the advent of neoadjuvant chemotherapy, radiotherapy and surgery alone were associated with a high risk of uncontrolled locoregional relapses in locally advanced breast cancer (LABC). MATERIAL AND METHODS: In the 1990s we initiated two neoadjuvant protocols, where patients with LABC were given either doxorubicin qW or 5-fluorouracil/mitomycin (FUMI) q3W to shrink the tumours prior to mastectomy and postoperative radiotherapy. Previously, we reported TP53 mutation status to predict a poor response to chemotherapy. Here, we present the long-term survival data, with a follow-up of 20 years in the doxorubicin (n = 90) and 15 years in the FUMI trial (n = 34). RESULTS: Patients in the doxorubicin trial with TP53-mutated tumours experienced a shorter recurrence-free (RFS; 14 vs. 83 months, p < 0.001) and overall survival (OS; 35 vs. 90 months, p < 0.001) than patients with TP53 wt tumours. Similarily, TP53 mutations were associated with a shorter OS (22 vs. 80 months, p = 0.03) and a tendency to shorter RFS (17 vs. 33 months, p = 0.06) in patients treated with FUMI. Furthermore, axillary lymph node metastases predicted shorter OS, but only in patients treated with doxorubicin (49 vs. 142 months, p < 0.04). Applying multivariate analysis, TP53 mutations predicted inferior RFS (p < 0.001) as well as OS (p < 0.001), independently of axillary lymph node status. Isolated local recurrences, without simultaneous distant metastases, occurred in seven patients only in the two trials. Interestingly, chest wall radiation fibrosis predicted improved OS (p = 0.004). CONCLUSION: TP53 inactivating mutations are associated with an inferior long-term prognosis in patients with LABC treated with conventional chemotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama
Genes p53
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Axila
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/genética
Neoplasias da Mama/mortalidade
Neoplasias da Mama/patologia
Doxorrubicina/uso terapêutico
Feminino
Fluoruracila/administração & dosagem
Seguimentos
Seres Humanos
Metástase Linfática
Meia-Idade
Mitomicinas/administração & dosagem
Terapia Neoadjuvante/métodos
Recidiva Local de Neoplasia/genética
Recidiva Local de Neoplasia/mortalidade
Prognóstico
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Mitomycins); 80168379AG (Doxorubicin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140610
[St] Status:MEDLINE
[do] DOI:10.3109/0284186X.2014.922215


  7 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24586407
[Au] Autor:Hoffman S; Martin D; Meléndez A; Bargonetti J
[Ad] Endereço:Department of Biological Sciences, Hunter College, City University of New York, New York City, New York, United States of America ; The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York City, New York, United States of America.
[Ti] Título:C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair.
[So] Source:PLoS One;9(2):e88828, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:p53 is a transcription factor that regulates the response to cellular stress. Mammalian p53 functions as a tumor suppressor. The C. elegans p53, cep-1, regulates DNA-damage induced germline cell death by activating the transcription of egl-1 and ced-13. We used the C. elegans model to investigate how, in the whole animal, different forms of DNA damage can induce p53-dependent versus p53-independent cell death and DNA repair. DNA damage was induced by ultraviolet type C (UVC) radiation, or 10-decarbamoyl mitomycin C (DMC, an agent known to induce mammalian p53-independent cell death). Wild-type or cep-1 loss-of-function mutant animals were assayed for germline cell death and DNA lesions. Wild-type animals displayed greater removal of UVC-lesions over time, whereas cep-1 mutant animals displayed increased UVC-lesion retention. The cep-1 mutation increased UVC-lesion retention directly correlated with a reduction of progeny viability. Consistent with DMC inducing p53-independent cell death in mammalian cells DMC induced a C. elegans p53-independent germline cell death pathway. To examine the influence of wild-type CEP-1 and DNA damage on C. elegans tumors we used glp-1(ar202gf)/Notch germline tumor mutants. UVC treatment of glp-1 mutant animals activated the CEP-1 target gene egl-1 and reduced tumor size. In cep-1(gk138);glp-1(ar202gf) animals, UVC treatment resulted in increased susceptibility to lesions and larger tumorous germlines. Interestingly, the partial knockdown of bec-1 in adults resulted in a CEP-1-dependent increase in germline cell death and an increase in DNA damage. These results strongly support cross-talk between BEC-1 and CEP-1 to protect the C. elegans genome.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/fisiologia
Reparo do DNA/fisiologia
Regulação da Expressão Gênica/genética
Proteína Supressora de Tumor p53/metabolismo
Proteínas de Transporte Vesicular/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/fisiologia
Caenorhabditis elegans/genética
Dano ao DNA/efeitos da radiação
Primers do DNA/genética
Reparo do DNA/genética
Células Germinativas/efeitos dos fármacos
Células Germinativas/fisiologia
Mitomicinas/farmacologia
Interferência de RNA
Proteínas Repressoras/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CEP-1 protein, C elegans); 0 (Caenorhabditis elegans Proteins); 0 (Ced-13 protein, C elegans); 0 (DNA Primers); 0 (EGL-1 protein, C elegans); 0 (Mitomycins); 0 (Repressor Proteins); 0 (Tumor Suppressor Protein p53); 0 (Vesicular Transport Proteins); 0 (bec-1 protein, C elegans); 26909-37-5 (10-decarbamoylmitomycin C)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140304
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0088828


  8 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23721078
[Au] Autor:Brucelle F; Renaud P
[Ad] Endereço:Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
[Ti] Título:Synthesis of a leucomitosane via a diastereoselective radical cascade.
[So] Source:J Org Chem;78(12):6245-52, 2013 Jun 21.
[Is] ISSN:1520-6904
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The preparation of trans-2,3-disubstituted indolines from 1-azido-2-allylbenzene derivatives via a diastereoselective radical cascade using ethyl iodoacetate and triethylborane is described. Further lactamization afforded substituted benzopyrrolizidinones with excellent diastereomeric ratios. The radical cascade/lactamization sequence was efficiently applied to the synthesis of a 3-oxo-leucomitosane related to the mitomycin family of alkaloids.
[Mh] Termos MeSH primário: Compostos Alílicos/química
Derivados de Benzeno/química
Indóis/síntese química
Mitomicinas/síntese química
[Mh] Termos MeSH secundário: Boranos/química
Iodoacetatos/química
Estrutura Molecular
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Allyl Compounds); 0 (Benzene Derivatives); 0 (Boranes); 0 (Indoles); 0 (Iodoacetates); 0 (Mitomycins); 300-57-2 (allylbenzene); Z3S980Z4P3 (triethylborane)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130601
[St] Status:MEDLINE
[do] DOI:10.1021/jo4009904


  9 / 6941 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:23654296
[Au] Autor:Bass PD; Gubler DA; Judd TC; Williams RM
[Ad] Endereço:Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
[Ti] Título:Mitomycinoid alkaloids: mechanism of action, biosynthesis, total syntheses, and synthetic approaches.
[So] Source:Chem Rev;113(8):6816-63, 2013 Aug 14.
[Is] ISSN:1520-6890
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Mitomicinas/biossíntese
Mitomicinas/síntese química
Mitomicinas/farmacologia
[Mh] Termos MeSH secundário: Técnicas de Química Sintética
Farmacorresistência Bacteriana
Mitomicina/química
Mitomicina/farmacologia
Oxazinas/síntese química
Oxazinas/farmacologia
Streptomyces/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Nome de substância:
0 (Mitomycins); 0 (Oxazines); 102363-08-6 (FR 900482); 50SG953SK6 (Mitomycin)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130510
[St] Status:MEDLINE
[do] DOI:10.1021/cr3001059


  10 / 6941 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23639828
[Au] Autor:Paz MM
[Ad] Endereço:Departamento de Química Orgánica, Facultade de Química, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain. manuel.paz@usc.es
[Ti] Título:Reductive activation of mitomycins A and C by vitamin C.
[So] Source:Bioorg Chem;48:1-7, 2013 Jun.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The anticancer drug mitomycin C produces cytotoxic effects after being converted to a highly reactive bis-electrophile by a reductive activation, a reaction that a number of 1-electron or 2-electron oxidoreductase enzymes can perform in cells. Several reports in the literature indicate that ascorbic acid can modulate the cytotoxic effects of mitomycin C, either potentiating or inhibiting its effects. As ascorbic acid is a reducing agent that is known to be able to reduce quinones, it could be possible that the observed modulatory effects are a consequence of a direct redox reduction between mitomycin C and ascorbate. To determine if this is the case, the reaction between mitomycin C and ascorbate was studied using UV/Vis spectroscopy and LC/MS. We also studied the reaction of ascorbate with mitomycin A, a highly toxic member of the mitomycin family with a higher redox potential than mitomycin C. We found that ascorbate is capable to reduce mitomycin A efficiently, but it reduces mitomycin C rather inefficiently. The mechanisms of activation have been elucidated based on the kinetics of the reduction and on the analysis of the mitosene derivatives formed after the reaction. We found that the activation occurs by the interplay of three different mechanisms that contribute differently, depending on the pH of the reaction. As the reduction of mitomycin C by ascorbate is rather inefficiently at physiologically relevant pH values we conclude that the modulatory effect of ascorbate on the cytotoxicity of mitomycin C is not the result of a direct redox reaction and therefore this modulation must be the consequence of other biochemical mechanisms.
[Mh] Termos MeSH primário: Ácido Ascórbico/química
Mitomicina/química
Mitomicinas/química
[Mh] Termos MeSH secundário: Animais
Células CHO
Sobrevivência Celular/efeitos dos fármacos
Cricetinae
Cricetulus
Concentração de Íons de Hidrogênio
Cinética
Mitomicina/toxicidade
Mitomicinas/toxicidade
Oxirredução
Quinonas/química
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitomycins); 0 (Quinones); 50SG953SK6 (Mitomycin); 87TMG6FJHV (mitomycin A); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130504
[St] Status:MEDLINE



página 1 de 695 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde