Hidantoínas e tio-hidantoínas n-substituídas: síntese, caracterização e estudo in silico para verificação de propriedades farmacocinéticas.

Abstract

The imidazolidines have been the subject of several studies because stand out by presenting a wide variety of biological activities such as antimicrobial, anticonvulsant, analgesic, sedative and antiparasitic. This work aimed to synthesize and characterize imidazolidines and thio-imidazolidines and perform in silico study for verification of some pharmacokinetic properties. First 12 aminoacids glycine derivatives were prepared by the Strecker synthesis, later they were treated with phenylisocyanate or phenylisothiocyanate, resulting in 24 imidazolidines which have their structures confirmed by infrared spectroscopy, Hydrogen Nuclear Magnetic Resonance (1H NMR) and Carbon (13C NMR ). To evaluate the pharmacokinetic properties of the synthesized imidazolidines, a computational study (in silico) was performed using the OSIRIS Property Explorer and Molinspiration programs. The in silico study showed that all compounds met the Lipinski rules. Studies have also shown that all tested imidazolidines are capable of being orally administered. Positive values of drug-score and drug-likeness indicate that’s molecules containing predominantly pharmacophoric groups which are commonly found in pharmaceutical products. The imidazolidines proved nontoxic, however, the in silico assessment of toxicity does not abolish the need for traditional toxicological testing. Analyzing the scores of bioactivity, it was observed that the G protein-coupled receptors is shown to be potential biological targets, it was tested for 11 imidazolidines. Only the compound HPA-19 had a positive value for the category of ion channel modulator. The favorable pharmacokinetic properties obtained in this study indicate the imidazolidines-2,4-diones and imidazoline-2-thioxo-4-ones N-substituted as potential new drug candidates.