Effects of quinoline-arylamidine hybrids on LPS-induced inflammation in RAW 264.7 cells
Background and purpose: Inflammation is a common pathogenesis in infection, injury, cancer, and many chronic diseases. Macrophages are among the main cells involved in generation of inflammation. The aim of the present study was to investigate the effects of molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible a 2-aminoethanol linker, on the in vitro inflammatory responses to lipopolysaccharides (LPS) induced inflammation in the RAW 264.7 cells.
Materials and methods: To determine effects of seven quinoline-arylamidine hybrids on the growth of the murine macrophage-like (RAW 264.7) cells MTT assay was used. Inflammatory reactions in the RAW264.7 cells were induced using E. coli lipopolysaccharides (LPS). Levels of nitric oxide (NO) and malondialdehyde (MDA) were determined by spectrophotometry methods. Intracellular production of reactive oxygen species (ROS) was measured by flow cytometry. Antioxidant capacity of tested compounds was tested by 2,2'-azino-bis(3-ethybenzthiazoline-6-sulfonic acid (ABTS) radical cation method.
Results: Tested hybrid compounds differentially influenced proliferation of non-stimulated and LPS-stimulated RAW 264.7 cells. The hybrid compounds have not presented ABTS radical-scavenger activity. In the LPS-stimulated RAW 264.7 cells 10 μM compounds slightly decreased production of NO and ROS and significantly modulated LPS-induced lipid peroxidation.
Conclusions: Molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible 2-aminoethanol linker markedly decreased accumulation of lipid peroxidation products in the LPS-stimulated RAW 264.7 cells. Further studies are necessary to determine their mechanism of anti-inflammatory action in more details.
Keywords: Hybrid molecules, 7-Chloroquinoline, Aromatic amidine, Anti-inflammatory activity in vitro
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