Design and Synthesis of Marine Polybrominated Diphenyl Ether Derivatives as Potential Anti-Inflammatory Agents.
Ning GaoCheng-Long GaoSha ChenMeng-Xue WangXu-Wen LiPublished in: Chemistry & biodiversity (2024)
Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.
Keyphrases
- lps induced
- molecular docking
- anti inflammatory
- inflammatory response
- induced apoptosis
- poor prognosis
- molecular dynamics simulations
- signaling pathway
- cell proliferation
- transcription factor
- human health
- toll like receptor
- south africa
- pi k akt
- long non coding rna
- immune response
- climate change
- endoplasmic reticulum stress