Avaliação da interação de compostos bioativos com carreador (sintético e natural) de fármacos

Abstract

About 70% of new synthetic molecules have low solubility in aqueous media, which can impair their bioavailability or even their use. In order to get around this problem, these compounds can be associated with macromolecules forming a drug-guest complex where multiple interactions can be involved. The present work evaluated the interaction of potential drugs, β-lapachone (βLP), 6CN10 (2-[(4-nitrophenyl)-amino]-4,5,6,7-tetrahydro-4H-benzo[β]thiophene-3-carbonitrile) and LQM10 (2-[(3,5-di-tert-butyl-4-hydroxyphenyl)methylene]hydrazinecarboximidamide), with PAMAMG3 (3rd generation polyamidoamine) and with BSA (bovine serum albumin). At first, a modified ITO electrode was used. The new electrode, built under ITO, was planned by electrodepositing gold nanoparticles (NPAu), cysteamine and PAMAMG3, resulting in ITO/NPAu/Cis/PAMAMG3. This system was characterized by visible ultraviolet spectroscopy (UV-Vis), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), Cyclic Voltammetry (VC), Differential pulse (VPD) and electrochemical impedance spectroscopy (ESI). Subsequently, by using VPD at pH 7.4, it was possible to evaluate the interaction of the PAMAMG3 dendrimer, a synthetic drug transport vehicle with the molecules under study. It was observed that there is encapsulation of substances by the dendrimer and it was possible to determine the interaction constant of the βLP-PAMAMG3 and LQM10-PAMAMG3 complex, being 1.42 x 106 L mol-1 and 3.33 x 105 mol L-1. By UV-Vis the constants were 2.00 x 103 L mol-1 and 2.50 x 103 mol L-1 for the βLP-PAMAMG3 and 6CN10-PAMAMG3 complexes. Considering that human serum albumin (HSA) is the main drug carrier within the body, a study was carried out on the interaction of these molecules with BSA, using molecular fluorescence and UV-Vis at pH 7.4. All complexes are formed by static quenching with formation of a non-fluorescent complex. The Kb value was 4.10 x 103, 1.69 x 103 and 3.31 x 106 L mol-1 for the BSA-βLP, BSA-6CN10 and BSA-LQM10 systems, respectively, which reveals greater affinity for protein by LQM10. According to thermodynamic parameters, electrostatic forces govern the interactions of βLP and LQM10 with the protein. The nitrocompound, on the other hand, mostly interacts by Van der Walls forces and hydrogen bonds. Three-dimensional fluorescence showed that there are conformational changes in the protein from interaction with the molecules. The biggest change is with the addition of LQM10. Showing that the greater the value of Kb, the greater the changes in the protein structure.