Suplementação de butirato para prevenção de diarreia e no desenvolvimento gastrointestinal e corporal de bezerros leiteiros

Abstract

Medicinal chemistry has great focus on search and obtaining of bioactive compounds, mainly on undiscovered chemical structures. Molecular hybridization, a synthetic strategy utilizing known bioactive structures, is a useful tool for obtaining substances with therapeutic potential. Through molecular hybridization tactic, union of bioactive structures with each other is possible, searching to refine and potentialize existing biological activity. Also, heterocycles being vastly distributed in structures of pharmaceutic drugs is known, seeing as great part of these drugs has at least one heterocyclic core. In fact, several heterocycles are known to be bioactive, among them thiazolidin-4-ones are an important and versatile core for molecular hybridization. These nuclei are obtained via one-pot reactions of easy material acquisition necessary for their synthesis. Compound 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) can be used for synthesis of analogues to synthetic antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT), given structural similarity between structures. With unification of 3,5-di-tert-butyl-4-hydroxybenzaldehyde to heterocycles, potential antioxidant activity for compounds can be expected. Antioxidant activity is vital when dealing with condition of oxidative stress, frequently linked to cancer and neurodegenerative diseases. In this work, a synthesis of 1,3-thiazolidin-4-one compounds analogous to BHT was developed and structures obtained were evaluated in free radical scavenging activity, an initial stage for attributing potential antioxidant activity. For this purpose, twelve novel 1,3-thiazolidin-4-ones analogous to BHT (4a-l) and one pyrazolo- [3,4-e] [1,4] thiazepin-7-one (5m) were obtained. Compounds were attained through one-pot reactions multicomponent tandem or stepwise in 24h, with use of 3,5-di-tert-butyl-4- hydroxybenzaldehyde (1), different primary amines (2a-m) and thioglycolic acid (3) with toluene reflux. After synthesis, pure compounds were properly identified and characterized by gas chromatography coupled with mass spectrometry (GC/MS) and nuclear magnetic resonance (NMR) spectroscopy (1H and 13C). Target compounds (4a-l, 5m) were obtained with high to low yields (84-28%). Reaction time remained the same for compounds derived from aliphatic and aromatic amines. Finally, molecules were tested by in vitro radical scavenging assays with DPPH• and ABTS•+ radicals. In these assays, three compounds showed noteworthy capacity to eliminate free radicals substantially superior (4d, 4b and 4a) to BHT and one compound slightly superior (4h) to BHT. In conclusion, synthesis presented may serve as basis to obtain 1,3- thiazolidin-4-ones carrying BHT moiety and be a starting point for development of new free radical scavenging structures.