Síntese de chalconas e bis-chalconas: estudo de moduladores de proteases que atuam na manutenção da hemostasia

Abstract

Pathologies related to disturbances of haemostasis and inflammation affect a large part of the world population. Among those illnesses, cardiovascular diseases such as cerebrovasculares diseases (CVD), ischemic heart disease, and cardiac failure are the main ones. Thus, the comprehension of the role and function of each biological structure in these mechanisms is fundamentally important, as well as the search for molecules able to modulate the components that act in these processes in an efficient and specific way, making the treatment and even healing of such diseases possible. Therefore, the research and synthesis of novel substances which show biological activities against inflammation and over haemostasis are of major importance. Chalcones and bis-chalcones are compounds that have shown a huge variety of pharmacological applications as anti-inflammatories, antioxidants, anticonvulsants, acetylcholinesterase inhibitors, antituberculosis, for cancer treatment, diabetes, etc. Furthermore, some characteristics of these molecules like simple synthesis pathways and high reaction yields make them targets of high interest for researchers all over the world. Additionally, the presence of hydrogens that can be replaced by several substituents provides an almost endless source of structures. In this work, four compounds were synthesized, which were 2 chalcone derivatives and 2 bis-chalcone derivatives. The synthesis were performed through Claisen-Schmidt condensation and the structures were characterized by Nuclear Magnetic Resonance (NMR). The biological properties of the molecules were evaluated by phospholipase, hemolytic, and clotting activities trials. The bis-chalcone derivative (1E,4E)- 1,5-bis(2-chlorophenyl)penta-1,4-dien-3-one showed good results retarding the clotting process and modulating the human phospholipid and erythrocyte degradation. Thus, this substance has the potential for application against cardiovascular diseases. However, more studies are needed to better understand its action mechanism.