Síntese, avaliação antibacteriana e estudo do perfíl farmacocinético, bioativo e de toxicidade do (2R)-3-butin-2-il 2,3,4,6-tetra-O-acetil-β-D- glicopiranosídeo

Abstract

Resistance to drugs against diseases caused by bacteria is increasing and becoming a growing public health problem. In this regard, O-glycosides, a class of molecules derived from natural carbohydrates, stand out due to their numerous biological applications, with emphasis on antibacterial activity. Thus, this work reports the synthesis, characterization, antimicrobial activity and in silico study of (2R)-3-butyn-2- yl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside. In the first reaction step, D-glucose was acetylated in 10 min and the product was obtained in a 90% yield. Next, penta- acetylated D-glucose was subjected to a glycosylation reaction with alcohol (2R)-3- butyn-2-ol, catalyzed by BF3•(OCH3)2, leading to the desired compound in 4.0 h, with a yield of 70% and excellent stereoselectivity (β:α = 97:3). The synthesized compounds were characterized by different techniques and the major product of the glycosylation reaction was determined by Hydrogen Magnetic Resonance (1H NMR). The inhibitory effect of (2R)-3-butyn-2-yl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside against S. aureus, S. Pyogenese, E. Faecalis, E. coli and K. pneumoniae was evaluated using the broth microdilution method. (2R)-3-butyn-2-yl 2,3,4,6-tetra-O-acetyl-β-D- glucopyranoside was active against the three tested strains, showing moderate activity against E. Faecalis (MIC: 1500 μg/mL) and S. aureus (MIC: 1000 μg/mL) and good activity against S. Pyogenesis (MIC: 500 μg/mL), E. coli (MIC: 500 μg/mL) and K. pneumoniae (MIC: 500 μg/ml). From these studies it was verified that the referred compound has a good availability for oral administration, since it did not disrespect any of Lipinski's parameters and had a high absorption in the gastrointestinal tract