Advisor | Peterson, Matt A. | |
Author | Oliveira, Marcélio de Moura | |
Access date | 2023-11-28T13:43:57Z | |
Available date | 2023-11-28T13:43:57Z | |
Document date | 2009 | |
Citation | OLIVEIRA, M. de Moura. Synthesis and Evaluation of N6,5'-Bis-Ureido-5'-Amino-5'-Deoxyadenosine Derivatives: Novel Nucleosides with Antiproliferative and Protein Kinase Binding Activities. 2009. Dissertação (Mestrado em Ciências) - Universidade Brigham Young, Utah, EUA, 2009. | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/61512 | |
Abstract in Portuguese | Uma nova série de derivados N6,5-bis-ureido-5-amino-5-desoxiadenosina foi preparada e avaliada quanto a atividades anticâncer usando o painel NCI 60 de cânceres humanos. Alguns dos derivados mostraram atividades promissoras (GI50 micromolares baixos) contra vários dos cancros representativos. Estas incluíram linhas celulares dos seguintes tipos de células gerais no NCI 60: cancro da leucemia, da mama, do sistema nervoso central, do pulmão de células não pequenas, do ovário, da próstata, do rim e do cólon. Compostos selecionados também foram avaliados quanto às suas afinidades com proteínas quinases. A síntese dos compostos foi simples e envolveu acilação de N6 com arilisocianatos, precedida por ativação e substituição nucleofílica da posição 5 para dar os derivados 5-azido-5-desoxiadenosina desejados. A redução da função 5-azido com H2/Pd-C ou Ph3P/H2O deu os produtos 5amino-5-desoxiadenosina desejados. A acilação do grupo 5-amino com N-metil 4nitrofenilcarbamato deu os produtos N6,5-bis-ureido-5-amino-5-desoxiadenosina. Os rendimentos variaram de bons (50–75%) a excelentes (75–95%) para todas as transformações sintéticas. | en_US |
Language | eng | en_US |
Rights | open access | en_US |
Subject in Portuguese | Agentes anticâncer | en_US |
Subject in Portuguese | N6 | en_US |
Subject in Portuguese | 5'-bis-ureido desoxiadenosina | en_US |
Subject in Portuguese | Proteínas quinases | en_US |
Title | Synthesis and evaluation of N6,5'-Bis-Ureido-5'-Amino-5'-Deoxyadenosine derivatives: novel nucleosides with Antiproliferative and Protein Kinase Binding Activities | en_US |
Type | Dissertation | en_US |
Defense date | 2009 | |
Departament | Department of Chemistry and Biochemistry. | en_US |
Defense Institution | Brigham Young University. Utah, EUA. | en_US |
Degree level | Mestrado Acadêmico | en_US |
Place of Defense | Utah, EUA | en_US |
Program | Physical and Mathematical Sciences; Chemistry and Biochemistry. | en_US |
Abstract | A new series of N6,5-bis-ureido-5-amino-5-deoxyadenosine derivatives was prepared and evaluated for anticancer activities using the NCI 60 panel of human cancers. Certain of the derivatives showed promising activities (low micromolar GI50’s) against several of the representative cancers. These included cell lines from the following general cell types in the NCI 60: Leukemia, Breast, Central Nervous System, Non-Small Cell Lung, Ovarian, Prostate, Renal, and Colon cancers. Select compounds were also screened for their affinities for protein kinases. The synthesis of the compounds was straightforward and involved N6 acylation with arylisocyanates, preceded by activation and nucleophilic substitution of the 5-position to give the desired 5-azido-5-deoxyadenosine derivatives. Reduction of the 5-azido function with either H2/Pd-C, or Ph3P/H2O, gave the desired 5amino-5-deoxyadenosine products. Acylation of the 5-amino group with N-methyl 4nitrophenylcarbamate gave the N6,5-bis-ureido-5-amino-5-deoxyadenosine products. Yields ranged from good (50–75%) to excellent (75–95%) for all synthetic transformations. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil. | en_US |
Subject | Anti-cancer agents | en_US |
Subject | N6 | en_US |
Subject | 5'-bis-ureido deoxyadenosine | en_US |
Subject | Protein kinases | en_US |
Member of the board | Peterson, Matt A. | |
Member of the board | Ham, Young Wan | |
Member of the board | Harrison, Roger G. | |