RESUMO
The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are repeating octasaccharide units consisting of monomers, dimers, and trimers. Pindolol is a beta-blocker used to treat cardiovascular disorders. We investigated the formation of complexes between pindolol and low-molecular-weight succinoglycan monomers (SGs). Even though SGs have a linear structure, the solubility of pindolol in the presence of SGs was increased up to 7-fold compared with methyl-ß-cyclodextrin reported as the best solubilizer of pindolol. Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Formation constants of complexes were determined from phase solubility diagrams. Conformation of complex was suggested based on a molecular docking study. The present study indicated that formation of pindolol/SGs complexes not only resulted in increased pindolol solubility but also could be useful for improving its clinical application as it did not affect cell viability.
Assuntos
Pindolol/química , Polissacarídeos Bacterianos/química , Antagonistas da Serotonina/química , Sinorhizobium meliloti/química , Varredura Diferencial de Calorimetria , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Modelos Moleculares , Peso Molecular , Pindolol/farmacologia , Polissacarídeos Bacterianos/metabolismo , Antagonistas da Serotonina/farmacologia , Sinorhizobium meliloti/metabolismo , Solubilidade , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Rhizobium leguminosarum produces unbranched cyclic ß-1,2-glucans, cyclosophoraoses (Cys). In the present study, Cys were modified with hydroxypropyl groups via a one step chemical derivatization and the complexation ability and solubility enhancement of hydroxypropyl cyclosophoraoses (HP Cys) with α-naphthoflavone (α-NF) were investigated. In the presence of HP Cys, the aqueous solubility of α-NF greatly increased up to 257-fold. Complex formation of HP Cys and α-NF was confirmed by nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR) spectroscopy, and differential scanning calorimetry (DSC). Furthermore, the morphological structure of α-NF with HP Cys was examined using scanning electron microscopy (SEM). A hypothetical model was proposed based on molecular dynamics (MD) simulations and a docking study of α-NF with HP Cys. Our results suggest that HP Cys form complexes with α-NF and can be utilized as a promising solubilizer. This is the first study to identify carbohydrates that can enhance the solubility of α-NF.
