RESUMO
Diamide linked γ-cyclodextrin (γ-CD) dimers are proposed as molecular-scale delivery agents for the anticancer agent curcumin. N,N'-Bis(6(A)-deoxy-γ-cyclodextrin-6(A)-yl)succinamide (66γCD2su) and N,N'-bis(6(A)-deoxy-γ-cyclodextrin-6(A)-yl)urea (66γCD2ur) markedly suppress the degradation of curcumin by forming a strong 1:1 cooperative binding complexes. The results presented in this study describe the potential efficacy of 66γCD2su and 66γCD2ur for intracellular curcumin delivery to cancer cells. Cellular viability assays demonstrated a dose-dependent antiproliferative effect of curcumin in human prostate cancer (PC-3) cells that was preserved by the curcumin-66γCD2su complex. In contrast, delivery of curcumin by 66γCD2ur significantly delayed the antiproliferative effect. We observed similar patterns of gene regulation in PC-3 cells for curcumin complexed with either 66γCD2su or 66γCD2ur in comparison to curcumin alone, although curcumin delivered by either 66γCD2su or 66γCD2ur induces a slightly higher up-regulation of heme oxygenase-1. Highlighting their nontoxic nature, neither 66γCD2su nor 66γCD2ur carriers alone had any measurable effect on cell proliferation or candidate gene expression in PC-3 cells. Finally, confocal fluorescence imaging and uptake studies were used to demonstrate the intracellular delivery of curcumin by 66γCD2su and 66γCD2ur. Overall, these results demonstrate effective intracellular delivery and action of curcumin when complexed with 66γCD2su and 66γCD2ur, providing further evidence of their potential applications to deliver curcumin effectively in cancer and other treatment settings.
Assuntos
Curcumina/química , Curcumina/farmacologia , Diamida/química , Neoplasias da Próstata/tratamento farmacológico , gama-Ciclodextrinas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Tripodal thioureas based on a cyclic peptide scaffold have been synthesised and their anion binding properties evaluated. These receptors show high affinity towards sulfate ions in aqueous solution.
Assuntos
Peptídeos Cíclicos/química , Sulfatos/química , Tioureia/química , Ligação de Hidrogênio , Íons/química , Água/químicaRESUMO
This critical review covers the developments in anion recognition and sensing using Zn(II)-dipicolylamine functionalized receptors over the past decade with emphasis on recent rapid advances in the last five years.
Assuntos
Aminas/química , Técnicas Biossensoriais/métodos , Técnicas de Química Analítica/instrumentação , Compostos Organometálicos/química , Ácidos Picolínicos/química , Zinco/química , Sequência de Aminoácidos , Animais , Ânions/análise , Ânions/química , Linhagem Celular , Humanos , Dados de Sequência MolecularRESUMO
Diamide linked γ-cyclodextrin (γ-CD) dimers are used to capture curcumin and suppress its decomposition in water. In this study, succinamide and urea linked γ-CD dimers joined through the C6(A) carbon on each γ-CD are used. The γ-CD dimers, 66γCD(2)su and 66γCD(2)ur, show a remarkable ability to suppress the decomposition of curcumin and extend its half-life from less than 30 min to greater than 16 h. The 1:1 association of curcumin with 66γCD(2)su and 66γCD(2)ur has high stability constants of 8.7 × 10(6) M(-1) and 2.0 × 10(6) M(-1), respectively. In addition, 2D (1)H NOESY NMR results show specific hydrogen interactions in the association of curcumin with 66γCD(2)su and 66γCD(2)ur, consistent with the cooperative binding of curcumin by both γ-CD annuli of 66γCD(2)su and 66γCD(2)ur. The interactions between curcumin in the linked γ-CD dimers and surfactant micelles were studied using fluorescence spectroscopy. While linked γ-CD dimer-bound curcumin has a negligible fluorescence quantum yield, a significant increase in fluorescence intensity (Φ(fl) > 2%) in the presence of micelles suggests that curcumin is delivered to the micelle. The overall results indicate that the diamide linked γ-CD dimers are highly promising systems for curcumin delivery in vivo due to effective curcumin stabilization.
