Base de dados : MEDLINE
Pesquisa : D02.455.526.728.650.050 [Categoria DeCS]
Referências encontradas : 87 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 9 ir para página                      

  1 / 87 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27473822
[Au] Autor:Trafalis D; Geromichalou E; Dalezis P; Nikoleousakos N; Sarli V
[Ad] Endereço:Laboratory of Pharmacology, Medical School National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece. Electronic address: dtrafal@med.uoa.gr.
[Ti] Título:Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics.
[So] Source:Steroids;115:1-8, 2016 Nov.
[Is] ISSN:1878-5867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/uso terapêutico
Lactamas/síntese química
Lactamas/uso terapêutico
Leucemia P388/tratamento farmacológico
Esteroides/síntese química
Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Mostarda de Anilina/química
Animais
Antineoplásicos/química
Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Feminino
Seres Humanos
Células Jurkat
Células K562
Lactamas/química
Lactamas/farmacologia
Masculino
Mecloretamina/química
Camundongos Endogâmicos BALB C
Esteroides/química
Esteroides/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Lactams); 0 (Steroids); 50D9XSG0VR (Mechlorethamine); CUJ6745Z9J (Aniline Mustard)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160731
[St] Status:MEDLINE


  2 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26769627
[Au] Autor:Chen CH; Hu TH; Huang TC; Chen YL; Chen YR; Cheng CC; Chen CT
[Ad] Endereço:Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617 Taiwan (R.O.C.), Fax: (+886) 2-23636359.
[Ti] Título:Delineation of G-Quadruplex Alkylation Sites Mediated by 3,6-Bis(1-methyl-4-vinylpyridinium iodide)carbazole-Aniline Mustard Conjugates.
[So] Source:Chemistry;21(48):17379-90, 2015 Nov 23.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new G-quadruplex (G-4)-directing alkylating agent BMVC-C3M was designed and synthesized to integrate 3,6-bis(1-methyl-4-vinylpyridinium iodide)carbazole (BMVC) with aniline mustard. Various telomeric G-4 structures (hybrid-2 type and antiparallel) and an oncogene promoter, c-MYC (parallel), were constructed to react with BMVC-C3M, yielding 35 % alkylation yield toward G-4 DNA over other DNA categories (<6 %) and high specificity under competition conditions. Analysis of the intact alkylation adducts by electrospray ionization mass spectroscopy (ESI-MS) revealed the stepwise DNA alkylation mechanism of aniline mustard for the first time. Furthermore, the monoalkylation sites and intrastrand cross-linking sites were determined and found to be dependent on G-4 topology based on the results of footprinting analysis in combination with mass spectroscopic techniques and in silico modeling. The results indicated that BMVC-C3M preferentially alkylated at A15 (H26), G12 (H24), and G2 (c-MYC), respectively, as monoalkylated adducts and formed A15-C3M-A21 (H26), G12-C3M-G4 (H24), and G2-C3M-G4/G17 (c-MYC), respectively, as cross-linked dialkylated adducts. Collectively, the stability and site-selective cross-linking capacity of BMVC-C3M provides a credible tool for the structural and functional characterization of G-4 DNAs in biological systems.
[Mh] Termos MeSH primário: Mostarda de Anilina/química
Carbazóis/química
Quadruplex G
Hidrocarbonetos Iodados/química
Compostos de Piridínio/química
[Mh] Termos MeSH secundário: Alquilação
DNA/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (1-methyl-4-vinylpyridinium); 0 (Carbazoles); 0 (Hydrocarbons, Iodinated); 0 (Pyridinium Compounds); 9007-49-2 (DNA); CUJ6745Z9J (Aniline Mustard)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:160115
[Lr] Data última revisão:
160115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160116
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201502595


  3 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:22546205
[Au] Autor:Çelik A; Yetis G
[Ad] Endereço:Gebze Institute of Technology, Department of Chemistry, 41400 Gebze-Kocaeli, Turkey. ayhancelik@gyte.edu.tr
[Ti] Título:An unusually cold active nitroreductase for prodrug activations.
[So] Source:Bioorg Med Chem;20(11):3540-50, 2012 Jun 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A set of PCR primers based on the genome sequence were used to clone a gene encoding a hypothetical nitroreductases (named as Ssap-NtrB) from uropathogenic staphylococcus, Staphylococcus saprophyticus strain ATCC 15305, an oxygen insensitive flavoenzyme. Activity studies of the translation product revealed that the nitroreductase catalyses two electron reduction of a nitroaromatic drug of nitrofurazone (NFZ), cancer prodrugs of CB1954 and SN23862 at optimum temperature of 20 °C together with retaining its maximum activity considerably at 3 °C. The required electrons for such reduction could be supplied by either NADH or NADPH with a small preference for the latter. The gene was engineered for heterologous expression in Escherichia coli, and conditions were found in which the enzyme was produced in a mostly soluble form. The recombinant enzyme was purified to homogeneity and physical, spectral and catalytical properties were determined. The findings lead us to propose that Ssap-NtrB represents a novel nitro reductase with an unusual cold active property, which has not been described previously for prodrug activating enzymes of nitroreductases.
[Mh] Termos MeSH primário: Nitrorredutases/metabolismo
Pró-Fármacos/metabolismo
Staphylococcus saprophyticus/enzimologia
[Mh] Termos MeSH secundário: Mostarda de Anilina/análogos & derivados
Mostarda de Anilina/metabolismo
Aziridinas/metabolismo
Clonagem Molecular
Eletroforese em Gel de Poliacrilamida
Estabilidade Enzimática
Escherichia coli/genética
Mononucleotídeo de Flavina/metabolismo
Concentração de Íons de Hidrogênio
Espectrometria de Massas
Nitrofurazona/metabolismo
Nitrorredutases/genética
Filogenia
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Staphylococcus saprophyticus/genética
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aziridines); 0 (Prodrugs); 0 (Recombinant Proteins); 142439-61-0 (5-(N,N-bis(2-chloroethyl)amino)-2,4-dinitrobenzamide); 7865D5D01M (tretazicar); 7N464URE7E (Flavin Mononucleotide); CUJ6745Z9J (Aniline Mustard); EC 1.7.- (Nitroreductases); X8XI70B5Z6 (Nitrofurazone)
[Em] Mês de entrada:1210
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120502
[St] Status:MEDLINE
[do] DOI:10.1016/j.bmc.2012.04.004


  4 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:21832047
[Au] Autor:Fedeles BI; Zhu AY; Young KS; Hillier SM; Proffitt KD; Essigmann JM; Croy RG
[Ad] Endereço:Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
[Ti] Título:Chemical genetics analysis of an aniline mustard anticancer agent reveals complex I of the electron transport chain as a target.
[So] Source:J Biol Chem;286(39):33910-20, 2011 Sep 30.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The antitumor agent 11ß (CAS 865070-37-7), consisting of a DNA-damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. The present study describes the unexpectedly strong activity of 11ß against the AR-negative HeLa cells, both in cell culture and tumor xenografts, and uncovers a new mechanism of action that likely explains this activity. Cellular fractionation experiments indicated that mitochondria are the major intracellular sink for 11ß; flow cytometry studies showed that 11ß exposure rapidly induced oxidative stress, mitochondria being an important source of reactive oxygen species (ROS). Additionally, 11ß inhibited oxygen consumption both in intact HeLa cells and in isolated mitochondria. Specifically, 11ß blocked uncoupled oxygen consumption when mitochondria were incubated with complex I substrates, but it had no effect on oxygen consumption driven by substrates acting downstream of complex I in the mitochondrial electron transport chain. Moreover, 11ß enhanced ROS generation in isolated mitochondria, suggesting that complex I inhibition is responsible for ROS production. At the cellular level, the presence of antioxidants (N-acetylcysteine or vitamin E) significantly reduced the toxicity of 11ß, implicating ROS production as an important contributor to cytotoxicity. Collectively, our findings establish complex I inhibition and ROS generation as a new mechanism of action for 11ß, which supplements conventional DNA adduct formation to promote cancer cell death.
[Mh] Termos MeSH primário: Mostarda de Anilina/farmacologia
Antineoplásicos Alquilantes/farmacologia
Complexo I de Transporte de Elétrons/antagonistas & inibidores
Complexo I de Transporte de Elétrons/metabolismo
Mitocôndrias Hepáticas/metabolismo
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Animais
Morte Celular/efeitos dos fármacos
Adutos de DNA/metabolismo
Feminino
Depuradores de Radicais Livres/farmacologia
Células HeLa
Seres Humanos
Masculino
Camundongos
Camundongos Nus
Estresse Oxidativo/efeitos dos fármacos
Consumo de Oxigênio/efeitos dos fármacos
Ratos
Espécies Reativas de Oxigênio/metabolismo
Vitamina E/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (DNA Adducts); 0 (Free Radical Scavengers); 0 (Reactive Oxygen Species); 1406-18-4 (Vitamin E); CUJ6745Z9J (Aniline Mustard); EC 1.6.5.3 (Electron Transport Complex I); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1111
[Cu] Atualização por classe:161202
[Lr] Data última revisão:
161202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110812
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M111.278390


  5 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:18450456
[Au] Autor:Kapuriya N; Kapuriya K; Zhang X; Chou TC; Kakadiya R; Wu YT; Tsai TH; Chen YT; Lee TC; Shah A; Naliapara Y; Su TL
[Ad] Endereço:Institute of Biomedical Sciences, Laboratory of Bioorganic Chemistry, Academia Sinica, Taipei 115, Taiwan.
[Ti] Título:Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
[So] Source:Bioorg Med Chem;16(10):5413-23, 2008 May 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To improve the chemical stability and therapeutic efficacy of N-mustard, a series of phenyl N-mustard linked to DNA-affinic 9-anilinoacridines and acridine via a urea linker were synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude mice against human tumor xenografts. It also showed that 24d was capable of inducing marked dose-dependent levels of DNA cross-linking by comet assay and has long half-life in rat plasma.
[Mh] Termos MeSH primário: Amsacrina/análogos & derivados
Mostarda de Anilina/síntese química
Mostarda de Anilina/farmacologia
Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Ureia/química
[Mh] Termos MeSH secundário: Acridinas/química
Amsacrina/química
Mostarda de Anilina/análogos & derivados
Animais
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
DNA/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Concentração Inibidora 50
Camundongos
Camundongos Nus
Estrutura Molecular
Ratos
Estereoisomerismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acridines); 0 (Antineoplastic Agents); 00DPD30SOY (Amsacrine); 3340-22-5 (9-anilinoacridine); 8W8T17847W (Urea); 9007-49-2 (DNA); CUJ6745Z9J (Aniline Mustard)
[Em] Mês de entrada:0808
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080503
[St] Status:MEDLINE
[do] DOI:10.1016/j.bmc.2008.04.024


  6 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:17085666
[Au] Autor:Mayer A; Francis RJ; Sharma SK; Tolner B; Springer CJ; Martin J; Boxer GM; Bell J; Green AJ; Hartley JA; Cruickshank C; Wren J; Chester KA; Begent RH
[Ad] Endereço:Department of Oncology, Hampstead Campus, University College London, UK. a.mayer@ucl.ac.uk
[Ti] Título:A phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody-enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug.
[So] Source:Clin Cancer Res;12(21):6509-16, 2006 Nov 01.
[Is] ISSN:1078-0432
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this study was to establish optimal variables for single administration of MFECP1, a recombinant antibody-enzyme fusion protein of an anti-carcinoembryonic antigen single-chain Fv antibody and the bacterial enzyme carboxypeptidase G2 followed by a bis-iodo phenol mustard prodrug. MFECP1 is manufactured in mannosylated form to facilitate normal tissue elimination. EXPERIMENTAL DESIGN: Pharmacokinetic, biodistribution, and tumor localization studies were used to test the hypothesis that MFECP1 localizes in tumor and clears from normal tissue via the liver. Firstly, safety of MFECP1 and a blood concentration of MFECP1 that would avoid systemic prodrug activation were tested. Secondly, dose escalation of prodrug was done. Thirdly, the dose of MFECP1 and timing of prodrug administration were optimized. RESULTS: MFECP1 was safe and well tolerated, cleared rapidly via the liver, and was less immunogenic than previously used products. Eighty-fold dose escalation from the starting dose of prodrug was carried out before dose-limiting toxicity occurred. Confirmation of the presence of enzyme in tumor and DNA interstrand cross-links indicating prodrug activation were obtained for the optimal dose and time point. A total of 28 of 31 patients was evaluable for response, the best response being a 10% reduction of tumor diameter, and 11 of 28 patients had stable disease. CONCLUSIONS: Optimal conditions for effective therapy were established. A study testing repeat treatment is currently being undertaken.
[Mh] Termos MeSH primário: Mostarda de Anilina/análogos & derivados
Antígeno Carcinoembrionário/imunologia
Neoplasias Colorretais/tratamento farmacológico
Pró-Fármacos/uso terapêutico
Proteínas Recombinantes de Fusão/uso terapêutico
gama-Glutamil Hidrolase/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Mostarda de Anilina/sangue
Mostarda de Anilina/farmacocinética
Mostarda de Anilina/uso terapêutico
Anticorpos Monoclonais/sangue
Anticorpos Monoclonais/uso terapêutico
Antineoplásicos/sangue
Antineoplásicos/farmacocinética
Antineoplásicos/uso terapêutico
Relação Dose-Resposta a Droga
Feminino
História do Século XVI
História do Século XVII
Seres Humanos
Imagem Tridimensional
Imunoconjugados/sangue
Imunoconjugados/farmacocinética
Imunoconjugados/uso terapêutico
Masculino
Pró-Fármacos/efeitos adversos
Pró-Fármacos/farmacocinética
Proteínas Recombinantes de Fusão/sangue
Proteínas Recombinantes de Fusão/farmacocinética
gama-Glutamil Hidrolase/sangue
gama-Glutamil Hidrolase/farmacocinética
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; HISTORICAL ARTICLE; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Carcinoembryonic Antigen); 0 (Immunoconjugates); 0 (Prodrugs); 0 (Recombinant Fusion Proteins); 1204-69-9 (hydroxyaniline mustard); CUJ6745Z9J (Aniline Mustard); EC 3.4.19.9 (gamma-Glutamyl Hydrolase)
[Em] Mês de entrada:0701
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:061107
[St] Status:MEDLINE


  7 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
[PMID]:15203171
[Au] Autor:Sharma U; Marquis JC; Nicole Dinaut A; Hillier SM; Fedeles B; Rye PT; Essigmann JM; Croy RG
[Ad] Endereço:Department of Chemistry and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
[Ti] Título:Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents.
[So] Source:Bioorg Med Chem Lett;14(14):3829-33, 2004 Jul 16.
[Is] ISSN:0960-894X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor.
[Mh] Termos MeSH primário: Compostos de Anilina/uso terapêutico
Antineoplásicos Alquilantes/síntese química
Neoplasias da Mama/tratamento farmacológico
Sobrevivência Celular/efeitos dos fármacos
Estradiol/uso terapêutico
[Mh] Termos MeSH secundário: Compostos de Anilina/química
Compostos de Anilina/farmacologia
Mostarda de Anilina
Antineoplásicos Alquilantes/farmacologia
Antineoplásicos Alquilantes/uso terapêutico
Sítios de Ligação
Neoplasias da Mama/metabolismo
Adutos de DNA/metabolismo
Relação Dose-Resposta a Droga
Desenho de Drogas
Estradiol/química
Estradiol/farmacologia
Estudos de Avaliação como Assunto
Feminino
Seres Humanos
Receptores Estrogênicos/metabolismo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Antineoplastic Agents, Alkylating); 0 (DNA Adducts); 0 (Receptors, Estrogen); 4TI98Z838E (Estradiol); CUJ6745Z9J (Aniline Mustard)
[Em] Mês de entrada:0502
[Cu] Atualização por classe:170219
[Lr] Data última revisão:
170219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040619
[St] Status:MEDLINE


  8 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:15115406
[Au] Autor:Niculescu-Duvaz I; Scanlon I; Niculescu-Duvaz D; Friedlos F; Martin J; Marais R; Springer CJ
[Ad] Endereço:Cancer Research-UK Centre for Cancer Therapeutics at the Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
[Ti] Título:Significant differences in biological parameters between prodrugs cleavable by carboxypeptidase G2 that generate 3,5-difluoro-phenol and -aniline nitrogen mustards in gene-directed enzyme prodrug therapy systems.
[So] Source:J Med Chem;47(10):2651-8, 2004 May 06.
[Is] ISSN:0022-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nine new nitrogen mustard compounds derived from 2,6-difluoro-4-hydroxy- (3a-e) and 2,6-difluoro-4-amino- (4a-d) aniline were synthesized as potential prodrugs. They were designed to be activated to their corresponding 3,5-difluorophenol and -aniline (4)-nitrogen mustards by the enzyme carboxypeptidase G2 (CPG2) in gene-directed enzyme prodrug therapy (GDEPT) models. The compounds were tested for cytotoxicity in the MDA MB-361 breast adenocarcinoma. The cell line was engineered to express stably either CPG2 tethered to the cell surface stCPG2-(Q)3 or beta-galactosidase (beta-Gal) as control. The cytotoxicity differentials were calculated between CPG 2-expressing and -nonexpressing cells and yielded different results for the two series of prodrugs despite their structural similarities. While the phenol compounds are ineffective as prodrugs, their aniline counterparts exhibit outstanding activity in the tumor cell lines expressing CPG2. [3,5-Difluoro-4-[bis(2-chloroethyl)amino]phenyl]carbamoyl-l-glutamic acid gave a differential of >227 in MDA MB361 cells as compared with 19 exhibited by 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-l-glutamic acid, 1a, which has been in clinical trials.
[Mh] Termos MeSH primário: Antineoplásicos/metabolismo
Ácido Glutâmico/metabolismo
Compostos de Mostarda Nitrogenada/metabolismo
Pró-Fármacos/metabolismo
gama-Glutamil Hidrolase/metabolismo
[Mh] Termos MeSH secundário: Mostarda de Anilina/análogos & derivados
Mostarda de Anilina/síntese química
Mostarda de Anilina/metabolismo
Mostarda de Anilina/farmacologia
Animais
Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Derivados de Benzeno/síntese química
Derivados de Benzeno/metabolismo
Derivados de Benzeno/farmacologia
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Terapia Genética
Ácido Glutâmico/análogos & derivados
Ácido Glutâmico/síntese química
Ácido Glutâmico/farmacologia
Meia-Vida
Seres Humanos
Camundongos
Transplante de Neoplasias
Compostos de Mostarda Nitrogenada/síntese química
Compostos de Mostarda Nitrogenada/farmacologia
Pró-Fármacos/síntese química
Pró-Fármacos/farmacologia
Relação Estrutura-Atividade
Transplante Heterólogo
gama-Glutamil Hidrolase/química
gama-Glutamil Hidrolase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 ((3,5-difluoro-4-(bis(2-chloroethyl)amino)phenyl)carbamoyl-glutamic acid); 0 (Antineoplastic Agents); 0 (Benzene Derivatives); 0 (Nitrogen Mustard Compounds); 0 (Prodrugs); 3KX376GY7L (Glutamic Acid); CUJ6745Z9J (Aniline Mustard); EC 3.4.19.9 (gamma-Glutamyl Hydrolase)
[Em] Mês de entrada:0406
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040430
[St] Status:MEDLINE


  9 / 87 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:15110346
[Au] Autor:Malik N; Luthra SK; Burke P; Price PM; Aboagye EO; Latigo J; Zhao Y; Brady F
[Ad] Endereço:Hammersmith Imanet, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
[Ti] Título:Radiosynthesis of 4-[(2-chloroethyl)(2-[(11)C]ethyl)amino]-phenoxycarbonyl-l-glutamic acid a half mustard prodrug as a potential probe for imaging antibody- and gene-directed enzyme prodrug therapy with positron emission tomography.
[So] Source:Appl Radiat Isot;60(6):825-34, 2004 Jun.
[Is] ISSN:0969-8043
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The potential antibody directed prodrug therapy half-mustard prodrug 4-[(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was synthesised by reductive alkylation of 4-[(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using acetaldehyde. 4-[(2-chloroethyl)[(11)C](2-ethyl)amino]phenoxycarbonyl-L-glutamic acid was synthesized with 18-22% decay corrected radiochemical yield in 45 min from EOB by reductive alkylation of 4-[(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using [(11)C]acetaldehyde. [(11)C]Acetaldehyde was prepared in 60% decay corrected radiochemical yield by oxidation of [(11)C]ethanol over heated copper oxide. The radiosynthesis of [(11)C]ethanol was re-examined and optimized. 4-[(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was found to have affinity for carboxypeptidase G2; the K(m) and V(max) were 99.4-115.9 microM (n=3) and 3.6-5.0 microM/min, respectively, at a carboxypeptidase G2 concentration of 0.0247 U/ml.
[Mh] Termos MeSH primário: Mostarda de Anilina/análogos & derivados
Mostarda de Anilina/síntese química
[Mh] Termos MeSH secundário: Acetaldeído
Mostarda de Anilina/farmacocinética
Indicadores e Reagentes
Marcação por Isótopo/métodos
Compostos Radiofarmacêuticos
Especificidade por Substrato
Tomografia Computadorizada de Emissão
gama-Glutamil Hidrolase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((4-(N,N-bis(2-chloroethyl)amino)phenoxycarbonyl)glutamic acid); 0 (Indicators and Reagents); 0 (Radiopharmaceuticals); CUJ6745Z9J (Aniline Mustard); EC 3.4.19.9 (gamma-Glutamyl Hydrolase); GO1N1ZPR3B (Acetaldehyde)
[Em] Mês de entrada:0406
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040428
[St] Status:MEDLINE


  10 / 87 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:15044963
[Au] Autor:Cheng TL; Liao KW; Tzou SC; Cheng CM; Chen BM; Roffler SR
[Ad] Endereço:School of Biomedical Science and Environmental Biology, and MedicoGenomic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
[Ti] Título:Hapten-directed targeting to single-chain antibody receptors.
[So] Source:Cancer Gene Ther;11(5):380-8, 2004 May.
[Is] ISSN:0929-1903
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Artificial recombinant receptors may be useful for selectively targeting imaging and therapeutic agents to sites of gene expression. To evaluate this approach, we developed transgenes to express highly on cells a single-chain antibody (scFv) against the hapten 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one (phOx). A phOx enzyme conjugate was created by covalently attaching phOx molecules to polyethylene glycol (PEG)-modified beta-glucuronidase. Cells expressing phOx scFv but not control scFv receptors were selectively killed after exposure to ss-glucuronidase derivatized with phOx and PEG (phOx-beta G-PEG) and a glucuronide prodrug (p-hydroxy aniline mustard beta-D-glucuronide, HAMG) of p-hydroxyaniline mustard. Targeted activation of HAMG produced bystander killing of receptor-negative cells in mixed populations containing as few as 10% phOx-receptor-positive cells. Functional phOx scFv receptors were stably expressed on B16-F1 melanoma tumors in vivo. Treatment of mice bearing established phOx-receptor-positive tumors with phOx-beta G-PEG and HAMG significantly (P< or =.0005) suppressed tumor growth as compared with treatment with beta G-PEG and HAMG or prodrug alone. phOx was unstable in the serum, suggesting alternative haptens may be more suitable for in vivo applications. Our results show that therapeutic agents can be targeted to artificial hapten receptors in vitro and in vivo. The expression of artificial receptors on target cells may allow preferential delivery of therapeutic or imaging molecules to sites of transgene expression.
[Mh] Termos MeSH primário: Mostarda de Anilina/análogos & derivados
Mostarda de Anilina/administração & dosagem
Anticorpos Monoclonais/imunologia
Sistemas de Liberação de Medicamentos
Melanoma/tratamento farmacológico
Neoplasias Experimentais/imunologia
Oxazóis/imunologia
Polietilenoglicóis/administração & dosagem
Pró-Fármacos/administração & dosagem
[Mh] Termos MeSH secundário: Mostarda de Anilina/síntese química
Mostarda de Anilina/imunologia
Animais
Anticorpos Monoclonais/genética
Linhagem Celular Tumoral
Expressão Gênica
Haptenos
Imunoterapia
Injeções Intravenosas
Melanoma/genética
Melanoma/imunologia
Camundongos
Neoplasias Experimentais/genética
Neoplasias Experimentais/terapia
Oxazóis/química
Polietilenoglicóis/síntese química
Pró-Fármacos/síntese química
Receptores de Superfície Celular/genética
Receptores de Superfície Celular/imunologia
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (4-ethoxymethylene-2-phenyl-2-oxazoline-5-one); 0 (Antibodies, Monoclonal); 0 (Haptens); 0 (Oxazoles); 0 (Prodrugs); 0 (Receptors, Cell Surface); 0 (Recombinant Proteins); 1204-69-9 (hydroxyaniline mustard); 30IQX730WE (Polyethylene Glycols); CUJ6745Z9J (Aniline Mustard)
[Em] Mês de entrada:0412
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040327
[St] Status:MEDLINE



página 1 de 9 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