Optimization and anti-inflammatory evaluation of methyl gallate derivatives as a myeloid differentiation protein 2 inhibitor.

In this study, we identified a novel compound 4k with the potent anti-inflammatory activity among 39 methyl gallate derivatives (MGDs). MGD 4k exhibited a high binding affinity to MD2, which in turn prevented the formation of the LPS/MD2/TLR4 complex. In addition, MGD 4k significantly reversed the upregulation of LPS-induced inflammatory mediators such as tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in vitro and in vivo. Mechanistically, MGD 4k performed anti-inflammatory function by inactivating JNK, ERK and p38 signaling pathways. Taken together, our study identified MGD 4k as a novel potential therapeutic agent for ALI through inhibiting MD2, inflammatory responses, and major inflammation-associated signaling pathways.
PMID: 31466835 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - August 18, 2019 Category: Chemistry Authors: Qiu Y, Xiao Z, Wang Y, Zhang D, Zhang W, Wang G, Chen W, Liang G, Li X, Zhang Y, Liu Z Tags: Bioorg Med Chem Source Type: research