Síntese e estudo da atividade antioxidante e antitumoral de compostos N,S - acetais utilizando biocatalisadores enzimáticos

Abstract

Biocatalysis research has grown exponentially in recent decades due to discoveries related to the synthesis of many compounds, mainly those with biological properties, which are beneficial to society. In addition, environmental concerns have led many research groups around the world, and even industries, to describe new synthetic protocols that are not harmful to the environmental and to considere the byproducts formed by reactions. Thus, the use of catalysts allows reactions more quickly using low-cost reagents and avoids the waste of solvents, which have a great impact on the environmental factor. In this sense, the use of enzymes has excellent catalytic characteristics such as high efficiency and biodegradation (instead of heavy metals); and in some cases, chemical transformations using enzymes occur in the aqueous medium, avoiding the use of polluting solvents. Many examples of enzymatic reactions have been described in the literature, and in view of the need to synthesize compounds in a more “green” way, interest arises in establishing a synthetic methodology for N,S-acetals, which are commonly found in a wide range of biological products with medical and biochemical applications. However, as far as we know, no other procedure has been described for the synthesis of N,S-acetals using biological catalysts, such as enzymes, other than the work reported by our own research group. In addition, the researchers are looking for a methodological innovation in reactors, which are greener and easier to handle. Thus, in this work, we proposed to use enzymes in the synthesis of some N,S-acetals under mild reaction conditions, besides to presenting an enzymatic reactor project based on the continuous flow chemistry applied in the synthesis of N,S-acetal. In this study, we proved that the LPP enzyme immobilization was effective and satisfactory and it was possible to reuse it in other cycles. The methods established using both free and immobilized enzymes proved to be tolerant for both thiol and amidosulfone, getting high yields in a short reaction time. In addition, N,S-acetals were evaluated to determine their antioxidant property and antitumor potential against the SK-MEL-19, SK-MEL-28, SK-MEL-103 and B16F10-Nex2 melanoma cell lines, and gratifying results were obtained with these assays.