Complexos do tipo hospedeiro-convidado a base de ciclodextrinas com promissora atividade anti-Tripanosoma cruzi

Abstract

In the present study, host-guest complexes were obtained using hydroxypropyl alpha, beta, and gamma cyclodextrins (HpaCD; HpBCD; HpγCD) for the encapsulation of two distinct molecules, a modified chalcone (CHC) and a modified coumarin (PCUM), aiming to test their anti-T. cruzi activities. Complexation with cyclodextrins was adopted due to the low water solubility of these molecules, representing a controlled release approach against Chagas disease. The CHC:HpBCD complexes were obtained through three different routes: lyophilization, mechanochemical method, and calcination. 1H NMR assays confirmed the inclusion of CHC in HpBCD in solution and provided the association constant of the complex, which is around 60. Differential thermal analysis and infrared spectroscopy evidenced the formation of a solid-state CHC complex with HpBCD for the mechanochemical method and calcination. Biological assays were performed for the complexes between CHC and HpbCD and demonstrated that the complex obtained via calcination showed antiparasitic activity against T. cruzi, with the advantage of better water solubility and requiring a lower mass quantity of CHC to act. Complexes between cyclodextrins and PCUM were produced via lyophilization and the mechanochemical method, resulting in 3 distinct complexes involving hydroxypropyl alpha, beta, and gamma cyclodextrins. Electrospray ionization mass spectrometry analyses indicated the formation of the complex only for alpha-cyclodextrin. Differential thermal analysis pointed to the formation of complexes with alpha and beta-cyclodextrin via the mechanochemical method for 12 hours. Thus, better encapsulation by HpaCD was demonstrated.