2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies

• DOI: 10.1016/j.ejmech.2016.04.028
• Publication Date: 2016-04-29T07:01:34Z
• Authors: Daniela Pires Gouvea; Flávia Aleixo Vas...; Gabriele dos Anjo...; Amilton Clair Pin...; Gerferson Fischer; Renata Parruca Sa...; Wanda Pereira Alm...; Wilson Cunico
• Keywords: Docking (animal); Anti-inflammatory

Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45-97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 μg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.