This study aimed to prepare a complex of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 6CN10, a poorly water soluble 2-aminothiophene derivative with antifungal properties, by freeze-drying technique. The complex was characterized by thermal analysis, infrared/Raman spectroscopy, X-ray diffraction and scanning electron microscopy. In addition, we used the data of the phase solubility study, 1H, and 2D NMR spectroscopy and molecular modeling in order to investigate the interactions between 6CN10 and HP-β-CD. The apparent solubility of 6CN10 with HP-β-CD increased more than 29 fold. The phase solubility assay in water at 25 ºC showed an AP-type curve, with an apparent stability constant K1:1 and K1:2 of 96 and 0.1989 M-1, respectively. The results of IR, NMR and docking indicate that 6CN10 is able to form complexes with HP-β-CD (1:1 and 1:2 stoichiometric ratios), generating the formation of inclusion and preferably, non-inclusion complexes. The antifungal activity against Cryptococcus neoformans demonstrated the superior performance of the complex (46.66 µg mL-1) when compared with the free drug (166.66-333.33 µg mL-1). The present study provides useful information for the potential application of complexation with low soluble compounds and about the type of complex formation between 6CN10 and HP-β-CD.
Keywords:
antifungal activity; inclusion complex; molecular modeling; NMR; solubility improvement
