RESUMO
The first example of conjugation of open-resorcinarenes with chlorambucil, ibuprofen, naproxen and indomethacin are presented. The cytotoxic properties of the obtained conjugates were tested against the cancer cell lines U-251, PC-3, K-562, HCT-15, MCF-7 and SKLU-1. It was found that the conjugate with chlorambucil, naproxen or indomethacin (having 8 moieties) was toxic towards cancer cell lines U-251 and K-562, with no activity against non-cancerous COS-7 cells. The conjugates with naproxen and indomethacin showed high selectivity towards U-251 tumor cells.
Assuntos
Antineoplásicos/farmacologia , Calixarenos/farmacologia , Fenilalanina/análogos & derivados , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Células COS , Calixarenos/síntese química , Calixarenos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fenilalanina/síntese química , Fenilalanina/química , Fenilalanina/farmacologia , Relação Estrutura-AtividadeRESUMO
METHODS: The synthesis of conjugates of flutamide with resorcinarene-PAMAM-dendrimers as well as alkyl and ethyl phenyl chains in the lower part of the macrocycle as a nucleus and diethylenetriamines in the dendritic branches gives the opportunity to obtain conjugates in one step of synthesis with 16 and 64 flutamide moieties in the structure. RESULTS: The in vitro anticancer studies showed that the conjugates of flutamide are more active than the free flutamide and the flutamide derivatives, thus diminishing the amount of flutamide used. The resorcinarenedendrimer- flutamide conjugates with a high drug payload improve the activity of the drug. CONCLUSION: This is important in delivering a sufficient amount of flutamide and suggests that the dendrimer facilitates more of the drug being introduced into cells. It was also observed that the new conjugates are less toxic than the anti-androgens.
Assuntos
Antineoplásicos/farmacologia , Calixarenos/farmacologia , Dendrímeros/farmacologia , Portadores de Fármacos/farmacologia , Flutamida/farmacologia , Fenilalanina/análogos & derivados , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Calixarenos/síntese química , Calixarenos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Flutamida/síntese química , Flutamida/química , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Fenilalanina/síntese química , Fenilalanina/química , Fenilalanina/farmacologiaRESUMO
Two sulfonated resorcinarenes were synthesized by reacting C-tetra(butyl) resorcinarene or C-tetra(2-(methylthio)ethyl)resorcinarene with formaldehyde in the presence of sodium sulfite. Their structures were determined via FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. Thermal gravimetric analyses of the derivatives were also carried out and revealed the presence of water molecules in the solid state. The sulfonated product of C-tetra(butyl)resorcinarene was characterized by an X-ray crystal structure determination. The asymmetric unit contains eight molecules of water and two of acetone, and analysis indicated that sulfonated resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the crystal array, classical hydrogen bond interactions O-H···O and intermolecular contacts were observed. In the crystal packing, a linear array of capsules of sulfonated resorcinarenes was generated for a chain of sodium atoms and sulfonate groups.
Assuntos
Alcanossulfonatos/síntese química , Calixarenos/síntese química , Formaldeído/química , Fenilalanina/análogos & derivados , Sulfitos/química , Acetona/química , Cristalografia por Raios X , Ligação de Hidrogênio , Conformação Molecular , Fenilalanina/síntese química , Solubilidade , Água/químicaRESUMO
Calixarenes, macrocyclic compounds of phenolic units linked by methylene groups at the 2,6-positions, present some of the requirements to serve as platforms for the design and synthesis of biological active compounds. They are also interesting host molecules for chemical biology study purposes. Their basic molecular scaffold has potential ability for molecule recognition; it is promptly synthesized in large amounts, and might be easily modified for maximizing molecular interactions toward relevant guest molecules. Calixarenes present well-defined conformational properties and cavities with molecular dimensions that enable to encapsulate guest drugs. Calixarenes have been shown to have antiviral, antibacterial, antifungal, and anticancer activities (including HIV as target). We provide here an overview of the use of calixarenes either as new chemical entity of distinct biological activities or as host for bioactive guest molecules. The importance of calixarenes for drugs development is discussed. The use of Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques for the study of calixarenes as biological molecule hosts is also described.