Abstract
AbstractChronic neuroinflammation is crucial in many neurodegenerative diseases, including AD. Neuroinflammation activates microglia, the CNS's central effector cells, and immune cells. Toxins and neuroinflammatory reactions can kill or damage neurons, activating microglial cells. Inflammatory mediators from activated microglia can kill neurons like cytokines, chemokines, reactive oxygen species, and reactive nitrogen species. Imidazo[1,2‐α]azines with different acid groups in position two of the heterocycle system were synthesized and tested as anti‐inflammatory and cell immunomodulators. We measured the ability of human neuroblastoma (SHSY‐5Y) and microglial (HMC3) cell lines to decrease PGE2 production under pro‐inflammatory conditions. All derivatives reduced PGE2 production. Inhibitory profiles indicate that compounds 8a and 8b are more effective and potent than 9a and 9b, indicating a steric effect of carboxyphenyl on imidazo[1,2‐α]azines, reducing their potency. However, imidazo[1,2α]pyrimidines (8b and 9b) with nitrogen at position 8 were less effective than those observed by other groups (8a, 9a, and 10a). imidazo[1,2‐α]pyrimidines are more polar due to nitrogen at position 8. The synthetically derivative imidazo[1,2‐α]pyridines decreased PGE2 formation in vitro on neural cells, microglia (HMC3), and neuroblastoma (SH‐SY5Y) cells, proving that they are more effective than imidazo[1,2‐α]pyrimidines. Two product esters selectively reduced HMC3 microglial cell PGE2 production. This finding may help develop neurodegenerative disease anti‐inflammatories.
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