Síntese de derivados da Boc-Alanina conjugados aos derivados da NPiperazina Alquilada como potenciais inibidores da lipase pancreática e da alfa-Amilase

Abstract

Obesity and type 2 Diabetes are chronic diseases with a high prevalence rate worldwide and are closely associated with the development of metabolic syndrome. Therefore, the understanding of their etiology and pathophysiology of these diseases is important for the application of prophylactic strategies, in addition to the identification of therapeutic targets. For example, pancreatic lipase and α-amylase enzymes are involved in the modulation of lipids and carbohydrates, respectively. This present work aimed to synthesize Boc-alanine derivatives with isomeric variation (L, D, and D, L) conjugated to the alkylated derivatives of N-piperazine and, subsequently, to evaluate their action through an in vitro assays against pancreatic lipase and α-amilase enzymes, through spectrophotometry. Eight derivatives of Boc-alanine were synthesized in conjunction with the alkylated derivatives of N-piperazine, among them, four Lenantiomers, two D-enantiomers and two racemic mixtures, these being structurally, new compounds. All of them had an effect on the pancreatic lipase and α-amylase enzymes, with emphasis on compounds 3b (L), 3c (L) and 4b (D) that presented IC 50 values: 26,48 ± 4,04; 96,20 ± 2,04 and 12,68 ± 1,53 µg/mL, respectively, which are lower than that of Orlistat (295,30 ± 11,22 µg/mL). For the α-amylase tests, the highlight was compound 4b (D), which presented an IC50 value of 134,50 ± 1,55 µg/mL, which is lower than that of Acarbose (448,30 ± 13,26 µg/mL). Therefore, the results demonstrated that Boc-alanine derivatives were able to inhibit lipase and α-amylase activity. Compound 4b was effective for both enzymes, representing a promising therapeutic agent for controlling the impact of metabolic disorders, including metabolic syndrome.