Research Information System
FEBS, Tours, France, 8 - 12 July 2023, vol.13, no.2, pp.103
Although various anti-inflammatory drugs are available, safer alternatives are required due to their severe side effects. The purpose of this study is to investigate the anti-inflammatory characteristics of a newly synthesized unique 1,2,3-triazole/ thiazolidinedione hybrid molecule named 4-((1-(3-nitrobenzyl)-4,5-dihydro-1H-1,2,3-triazo-4-yl)methoxy)benzohydrazide. The impact of this hybrid compound on macrophages and neuroblastoma cells was examined to determine its anti-inflammatory characteristics. THP-1 cells were first stimulated for 24 hours with 160 nM phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages. A 9.71-fold increase in MMP9 expression detected by qRT-PCR was interpreted as confirmation of differentiation. In addition, every 2 hours, morphological changes were recorded by Cytosmart Lux3 Fl. After the determination of nontoxic doses of the compound, both macrophages and neuroblastoma cells were treated with 0.025 mM 4-((1-(3-nitrobenzyl)-4,5- dihydro-1H-1,2,3-triazolyl)methoxy)benzohydrazide for 24 hours, and the expression of a particular group of genes (IFNG, IL6, IL1B, TNFa, BACT, and NFKB1) that play a role in the inflammatory pathways was determined by qRT-PCR. Macrophages were pretreated with 1 lg/mL lipopolysaccharide for 24 hours before being treated with the drug. Although 4-((1-(3- nitrobenzyl)-4,5-dihydro-1H-1,2,3-triazol-4-yl)methoxy)benzohydrazide had no significant effect on TNFa, IL6, or NFKB1 expression in macrophages; it did reduce IL1B and IFNG expression significantly. Given the promising preliminary data, these findings suggest that it has anti-neuroinflammatory properties without negligible cytotoxicity. Nonetheless, investigations are still being conducted to investigate the compound’s genuine anti-neuroinflammation activities in the coculture of neuroblastoma and macrophage cells.