Síntese e caracterização de compostos n-heterociclicos substituídos e triagem in vitro do potencial antibacteriano e modulador enzimático

Abstract

In this moment, multicomponent reactions are extremely relevant inside green chemistry, being used for many organic modifications, as well as for extending and increasing the library of biologically active compounds. Furthermore, multicomponent reactions allow the construction of several bonds and reactions in a sequence, without the need to isolate the intermediates and without changing the reaction conditions. Due to their flexibility, high yield, lower energy expenditure, low process waste and low production cost, these reactions offer notable advantages over traditional synthesis. An additional and very important need for ecological solvents or even the non-use of them avoiding environmental pollution. In recent years, special attention has been given to the synthesis of polyhydroquinolines due to their high pharmacological potential. Some derivatives of this class were synthesized without use of catalysts or solvents either. For the characterization of these molecules, 1H and 13C nuclear magnetic resonance analyzes and spectroscopy in the infrared region, with Fourier transform were performed, and the results demonstrate that the molecules were successfully synthesized, in addition to showing antimicrobial activity, and in the technique of serial dilution, the molecules showed statistically significant results both for Staphylococcus aureus ATCC 25923 and for Pseudomonas aeruginosa ATCC 27853, with significant bactericidal action. The molecules had no effect on citrated human plasma, but were able to increase the clotting time, induced by Bothrops moojeni venom, when previously incubated with the plasma. Previous incubation of the molecules with B. moojeni venom reduced the thrombolytic activity of the venom. For phospholipase activity, doses previously incubated with the same venom resulted in inhibitions close to 30% or more. The molecules were also able to reduce signicantly the cytotoxicity induced by proteases and phospholipases A2 present in venom at the doses tested. Thus, the synthesized polyhydroquinoline derivatives proved to be easy to obtain and in accordance with the standards of green chemistry, in addition to presenting several biological properties that highlight their pharmaceutical potential.