RESUMO
A possible way of improving the activity and selectivity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules. Thus, four resorcinarene-PAMAM-dendrimer conjugates of chlorambucil with different groups in the lower part of the macrocycle and different length dendritic arms showed a good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the resorcinarene-PAMAM-dendrimer-chlorambucil conjugate employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) demonstrated that the conjugate was more potent as an antiproliferative agent than chlorambucil.
Assuntos
Antineoplásicos/administração & dosagem , Calixarenos/química , Clorambucila/administração & dosagem , Portadores de Fármacos/química , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Fenilalanina/análogos & derivados , Dendrímeros/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Fenilalanina/químicaRESUMO
p-[bis(chloro-2-ethyl)amino]-L-phenylalanine (melphalan) is an approved anti-cancer agent with a broad spectrum of antitumor activity. However, it has some disadvantages, such as poor water-solubility followed by rapid elimination, which reduce the target specificity. To solve these problems, porphyrin- poly(amidoamine) or PAMAM-conjugates of melphalan were synthesized and characterized. The dendrimeric conjugates showed satisfactory water solubility. It was found that the size of the dendrimer played a crucial role in controlling the drug content and diameter of the melphalan-conjugates. The in vitro studies of cell cytotoxicity revealed that by employing the dendrimeric conjugation strategy and using the PAMAM dendritic arms as spacers, the conjugates had good anti-cancer activity and lower toxicity than free melphalan.
Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Portadores de Fármacos/química , Melfalan/farmacologia , Porfirinas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Solubilidade , Água/químicaRESUMO
Dendrimers bearing pyrene donor groups have been obtained and act as efficient light-harvesting antennae capable of transferring light energy through space from their periphery to their core. The light-harvesting ability increases with each generation due to an increase in the number of peripheral pyrenes. In order to evaluate the photovoltaic properties of the compounds, thermal evaporated thin films were produced and the voltage response in the presence of visible light was obtained. The energy transfer efficiency was found to be almost quantitative for the first and second generations. The dendrimers have the potential to become integral components of molecular photonic devices.
Assuntos
Dendrímeros/síntese química , Porfirinas/química , Pirenos/química , Dendrímeros/química , Eletroquímica , Transferência de Energia , Complexos de Proteínas Captadores de Luz , Estrutura MolecularRESUMO
Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been synthesized. The first and second generations of these porphyrin-PAMAM-fluorene dendrimers were characterized by 1H-NMR, 13C-NMR, FTIR, UV-vis spectroscopy, elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra showed that the individual properties of donor and acceptor moieties were preserved, indicating that the new dendrimers could be used as photosynthetic antennae. Furthermore, for fluorescent spectroscopy, these dendrimers showed good energy transfer.
Assuntos
Dendrímeros/síntese química , Corantes Fluorescentes/síntese química , Porfirinas/química , Dendrímeros/química , Corantes Fluorescentes/química , Ressonância Magnética Nuclear Biomolecular , Poliaminas/química , Porfirinas/síntese química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
BACKGROUND: One of the possible ways of improving the activity and selectivity profile of anticancer agents is to design drug carrier systems employing nanomolecules. Calix[4]arene derivatives and chlorambucil and ibuprofen are important compounds that exhibit interesting anticancer properties. OBJECTIVE: The objective of this article is the synthesis of new calix[4]arene-derivative conjugates of chlorambucil or ibuprofen with potential anticancer activity. METHODS: Cytotoxicity assays were determined using the protein-binding dye sulforhodamine B (SRB) in microculture to measure cell growth as described [19, 20]. Conjugates of chlorambucil and resorcinarene-dendrimers were prepared in 2% DMSO and added into the culture medium immediately before use. Control cells were treated with 2% DMSO. RESULTS: Thus, calix[4]arene-derivative conjugates of chlorambucil or ibuprofen showed good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the calix[4]arene chlorambucil or ibuprofen conjugates employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) and U-251 (human glioblastoma cells) demonstrated that the conjugate was more potent as an antiproliferative agent than free chlorambucil and ibuprofen. The conjugates did not show any activity against the COS-7 African green monkey kidney fibroblast cell line. CONCLUSION: In the paper, we report the synthesis and spectroscopic analyses of new calix[4]arene derivative conjugates of chlorambucil or ibuprofen. Cytotoxicity assays revealed that at 10 µM, the conjugates were very active against K-562 (human chronic myelogenous leukemia cells) and U- 251 (human glioblastoma cells) cancer cells' proliferation. In order to explain the molecular mechanisms involved in the anticancer activity of calix[4]arene chlorambucil or ibuprofen conjugates, our research will be continued.