Síntese de tiazolidinonas derivadas da 1-(2-aminoetil) pirrolidina e estudo da atividade antimicrobiana

Abstract

Twenty-two 1,3-thiazolidin-4-ones were synthesized from 1-(2-aminoethyl) pyrrolidine, arenaldehydes substituted at the ortho, meta and para (NO2, F, Cl, OCH3, CH3, and OH ) and mercaptoacetic acid. These thiazolidinones were synthesized by one-pot methodology using conventional thermal heating in a Dean Stark trap for azeotropic removal of water. The reaction occurred at 5 hours with the initial formation of the intermediate imine followed by an intramolecular cyclization to the products. All substances are novel in the literature and were identified by mass spectrometry (GC-MS), nuclear magnetic resonance 1H and 13C (NMR) and five of them by high resolution mass spectroscopy (HRMS). In addition, alternative methodologies were studied using ultrasound and microwave searching for a reduction in the reaction time through one-pot and multicomponent reactions. All synthesized compounds have been evaluated their antimicrobial activity against fungi (Candida albicans, C. parapsilosis, C. glabrata, C. lipolytica, C.famata), and bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas aeuruginosa), using the broth microdilution bioassay. The results were reported in values inhibit growth by 50% (IC50). The compound 4-CH3 showed the better antifungal activity of the series with IC50 value (7,81 µg/mL) and high selectivity by the fungus Candida parapsilosis. On the other hand, Compound 2-F broad sweep showed antifungal activity and is considered the most potent antifungal. The cytotoxicity of thiazolidinones were evaluated in NIH/3T3 fibroblast cells exposed mice for 24 and 48 h each compound, with data expressed as mean ± SEM and considering the value of p <0,05 as a significant difference, analyzing the data using Tukey's test. In general, the compounds did not show cytotoxic at the concentrations of 250 µg/mL when compared to control.