IMMUNOMODULATORY ACTIVITY OF SYNTHETIC AURONE DERIVATIVES, AZAAURONES, IN LPS-STIMULATED RAW 246.7 MACROPHAGE-LIKE CELLS

dc.contributor.advisor Farone, Anthony
dc.contributor.author alrayes, zahrah
dc.contributor.committeemember Farone, Mary
dc.contributor.committeemember Kline, Paul
dc.contributor.committeemember Miller, Justin
dc.date.accessioned 2024-05-07T16:02:24Z
dc.date.available 2024-05-07T16:02:24Z
dc.date.issued 2024
dc.date.updated 2024-05-07T16:02:24Z
dc.description.abstract Inflammation, a fundamental biological response, is essential for various physiological processes. However, dysregulated or chronic inflammation is linked to numerous pathological conditions. This thesis delves into the unexplored realm of azaaurone derivatives, nitrogen-substituted versions of aurones, investigating their potential as anti-inflammatory agents. The research comprises two distinct chapters, each shedding light on different facets of the anti-inflammatory properties of azaaurones. In the first experiment, titled "Evaluation of Twenty-Seven Azaaurone Derivatives as Potential Anti-Inflammatory Agents," a screening of 27 azaaurones for cytotoxicity in RAW 264.7 cells, a murine macrophage-like cell model, was conducted. Four promising derivatives (AAA2Me, AAA3Br, AAAPh and AAA3Me) were identified as showing minimal cytotoxicity. Subsequent treatments of the macrophage-like cells demonstrated a dose-dependent reduction in nitrite production, with AAAPh and AAA3Me exhibiting notable inhibitory effects. Importantly, azaaurones displayed anti-inflammatory potential at concentrations approximately 40 times lower than aurones, highlighting their considerable bioactivity. In the second experiment, titled "The Effects of the Synthetic Azaaurone (Z)-1-Acetyl-2- Benzylideneindolin-3-one on iNOS, NF-κB, and MAPK Pathways in LPS-Stimulated RAW 264.7 Cells," the focus shifted to (Z)-1-Acetyl-2-Benzylideneindolin-3-one and its derivatives. The study assessed iNOS protein expression, NF-κB and MAPK pathway activation, and TNF-α secretion in LPS-stimulated RAW 264.7 cells. While azaaurones did not significantly reduce iNOS protein expression, they demonstrated promising effects on inflammation-associated signaling pathways. Notably, AAA2Me showed a significant reduction in p38 protein expression, indicating a potential mechanism of action. Additionally, a trend towards decreased pp38 and reduced TNF-α secretion by multiple derivatives further supports their anti-inflammatory efficacy. These findings collectively underscore the considerable anti-inflammatory potential of azaaurone derivatives, positioning them as promising candidates for further drug development. The significant inhibition observed at low concentrations, coupled with insights into their molecular interactions and impact on key signaling pathways, provides a solid foundation for future research and therapeutic applications targeting inflammatory responses. The potential of azaaurones to address chronic inflammation and associated diseases opens up new possibilities for advancing drug discovery and improving clinical outcomes.
dc.description.degree Ph.D.
dc.identifier.uri https://jewlscholar.mtsu.edu/handle/mtsu/7208
dc.language.rfc3066 en
dc.publisher Middle Tennessee State University
dc.source.uri http://dissertations.umi.com/mtsu:11866
dc.subject Immunology
dc.thesis.degreelevel doctoral
dc.title IMMUNOMODULATORY ACTIVITY OF SYNTHETIC AURONE DERIVATIVES, AZAAURONES, IN LPS-STIMULATED RAW 246.7 MACROPHAGE-LIKE CELLS
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