Novas imidas derivadas de safrol: estudo antibacteriano e computacional para verificação de propriedades farmacocinéticas.

Abstract

The cyclic imides have been the subject of several studies, for stand out for having a wide variety of biological activities, such as antifungal, antibacterial and insecticide. This work aimed to study some cyclic imides obtained, making their computational analysis and study of its antibacterial activities and determination of some pharmacokinetic properties in silico. In the study five compounds were used: 1- (19-bromo-18-nitrophenyl) -11,12 methylendioxy-5-methyl-3,4,5,6-tetrahydronaphthalene-2,15-dicarboxyimide (NII-Br); 1-Benzyl-11,12-methylenedioxy-5-methyl-3,4,5,6-tetrahydronaphthalene-2,15-dicarboxyimide (NII-Bz); 11,12-methylenedioxy-5-methyl-3,4,5,6-tetrahydronaphthalene-2,15-dicarboxylic acid anhydride (NII-OO); 1- (11,12-methylenedioxy-5-methyl-3,4,5,6-tetrahydronaphthalene-2,15-dicarboxyimide) -para-benzosulfonilamine (NII-SO2); e 1- (19-fluoro-18-nitrophenyl) -11,12 methylendioxy-5-methyl-3,4,5,6-tetrahydronaphthalene-2,15-dicarboxyimide (NII-F). In the study of antibacterial activity against E. coli, S. pyogenes and S. pneumoniae none of the compounds was effective. To evaluate the pharmacokinetic properties of the cyclic imides, there was a computational study (in silico) through OSIRIS Property Explorer and Molinspiration programs. The in silico study showed that all compounds met the rules of Lipinski. Studies also show that all tested imides are suitable to be administered orally. Positive values of drug-score and drug-likeness indicate that the molecules contain predominantly pharmacophoric groups which are commonly encountered in pharmaceuticals. Imides no risk of toxicity, with the exception of NII-Br showed that mutagenic potential, however the assessment in silico toxicity does not extinguish the need for traditional toxicological testing. Analyzing the bioactivity scores, it is concluded that the G protein-coupled receptors were shown to be potential biological targets for NII-Bz compound; the NII-Br compound was as a possible protease inhibitor; and NII-SO2 as an enzyme inhibitor. The theoretical data obtained in the study indicate some of cyclic imides tested as potential candidates for new drugs.