Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents.
作者： Jingjie Bi , Wenqing Wang , Junxi Du , Kun Chen , Kui Cheng
DOI: 10.1016/J.EJMECH.2019.06.059
关键词: Nitric oxide 、 Alkaline phosphatase 、 Inflammation 、 TLR2 、 Peripheral blood mononuclear cell 、 Cytokine 、 Molecular biology 、 Viability assay 、 Chemistry 、 Tumor necrosis factor alpha
摘要: Abstract A series of S-allyl- l -cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited most potent inhibitory activity to Pam 3 CSK 4 -induced nitric oxide (NO) in RAW264.7 macrophages IC 50 22.54 ± 2.60 μM. The structure-activity relationship (SAR) study suggested that esterified carboxyl group, carbon chain extension methoxylation phenol hydroxy could improve efficacy. Preliminary mechanism studies showed significantly down-regulated levels triggered TNF-α cytokine human THP-1 cells, mouse RAW 264.7 macrophages, well ex-vivo peripheral blood mononuclear cells (PBMC) no influence on cell viability. specifically blocked ignited secreted embryonic alkaline phosphatase (SEAP) signaling Poly I:C or LPS TLR3 TLR4 signaling. Moreover, suppressed TLR2 HEK-Blue hTLR2 inhibited formation TLR1-TLR2, TLR2-TLR6 complex PBMC. In summary, pathway down-regulate inflammation cytokines, such NO, SEAP TNF-α, realize its activity.
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