Prospecção in vitro de polihidroquinolinas sintetizadas: atividade antimicrobiana e potencial modulador sobre enzimas que atuam em processos hemostáticos e inflamatórios

Abstract

The presence of nitrogen and/or aromatic rings in molecules is evidenced in several active principles of chemicals used in medicine, pharmacology, and agrochemistry. Quinolines are part of the alkaloids group (organic compounds, found mainly in plants, which have nitrogen in their structure). Polyhydroquinolines (PHQs) are asymmetric derivatives of 1,4-dihydropyridines, cyclic 1,3-dicetones, aldehydes, ethyl acetoacetate, and ammonium acetate, and are considered to be analogues of NADH. They also have several medicinal properties. In the development of new pharmacological substances, the organic synthesis is directly linked to molecules and components previously isolated from natural products. Currently, epidemiological data highlight the worldwide prevalence and growth of diseases related to obesity and overweight, and these have origin and/or inflammatory development as well as are associated with various changes in hemostasis. Thus, the development of protocols for the synthesis of molecules that present biological activities previously described and that are relatively simple and inexpensive is of extreme importance to obtain effective drugs accessible to most populations. Thus, in this work a simple, effective, and reliable multicomponent reaction was used to effectively synthesize the molecules 4-(4-hydroxy-phenyl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethyl ester and 4-(2-chloro-phenyl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethyl ester. The synthesized molecules were evaluated in vitro and the results showed that both showed biological activities (effects on erythrocyte membranes, on blood plasma coagulation, on human thrombi, and antimicrobial activity). In addition, the molecules were also evaluated for their modulating effects on enzymes (phospholipases A2 and proteases) that act in hemostatic (hemolysis, blood coagulation, fibrinogenolysis, and thrombolysis) and inflammatory processes (generation of eicosanoids that act in the inflammatory response, coagulation, and platelet aggregation). Thus, it is proven the effectiveness of the synthesis and usefulness of the compounds.