Síntese e avaliação do efeito citotóxico de 4-aminoquinolinas contendo substituintes iminícos

Abstract

In medicinal and synthetic chemistry, the quinoline nucleus, which is found in many structures of natural products and synthetic drugs, play an important role in the synthesis of new bioactive molecules. This role is mainly due to the numerous pharmacological activities that the quinoline nucleus presents, such as antimalarial, fungicide, bactericide, leishmanicide, anti-inflammatory, among many others. Schiff bases are imines, generally aromatic, which have also been shown to contain several interesting biological properties, especially anti-inflammatory, antimicrobial, antiprotozoal, antioxidant, anticonvulsant, anticancer, and antituberculosis activities. In this context, the present work aimed to synthesize a series of 4-aminoquinolines, which is already a known pharmacophoric group, now containing imine substituents and assessing its toxic effect for investigating antimalarial potential and leishmanicidal activity. Considering the synthesis of these derivatives, it was necessary to prepare first the following compounds: N-(2-aminoethyl)-7-chloroquinolin-4-amine (CEQ) and N-(7-chloroquinolin-4-yl) benzene-1,4-diamine (CPPQ). After that, the 4-aminoquinoline derivatives were dissolved in ethanol, homogenized under stirring with the aromatic aldehyde of interest, and the reaction mixture was heated under reflux for a maximum of 6 hours. The products were purified by recrystallization and vacuum dried. 18 compounds were synthesized and characterized by 1H, 13C and IV NMR spectroscopic methods. In the analysis of the results it was possible to confirm the formation of 11 imine aminoquinolines (AMQIs), which presented yields between 37 and 78%. The evaluation of the cytotoxic effect (MTT) showed, in general, that the AMQIs tested showed maximum toxic effect at concentrations of 50 or 100 M. That the compound AMQI4 had the highest CC50 value being the least toxic and AMQI7 the most toxic. The structural modifications promoted in the synthesized analogs did not show significant changes in the toxic effect of the compounds, however, despite the cytotoxicity observed in the results, it is necessary to carry out cell selectivity tests in order to observe whether the compounds can be selective against a cell line in which would make them viable for future pharmacological use.