Design, synthesis and anti-inflammatory activity of diterpenoid alkaloids and non-steroidal anti-inflammatory drug hybrids based on molecular hybridization strategy

In this study, we synthesized 25 diterpenoid alkaloid derivatives with NSAIDs, organized into four series. Among these derivatives, lappaconitine derivative 1e demonstrated the strongest inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells with minimal cytotoxicity. Additionally, 1e effectively suppressed the inflammatory response induced by carrageenan in vivo, with a swelling rate of only 1%. This anti-inflammatory potency was found to be significantly superior to that of naproxen. The molecular docking analysis revealed that the binding affinity of 1e was scored as -10.3 kcal/mol, suggesting that it forms a stable complex with cyclooxygenase-2 (COX-2). Therefore, compound 1e holds potential as a lead anti-inflammatory compound that could be further developed.PMID:37164150 | DOI:10.1016/j.fitote.2023.105536
Source: Fitoterapia - Category: Biochemistry Authors: Source Type: research