Design and synthesis of new N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides as anti-inflammatory agents

Twenty-four new dipeptide analogs (1–24) of aurantiamide acetate were designed, synthesized, and assayed for effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, seven N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides (6, 9, 12, 14, 17, 18 and 20) showed potent inhibitory effects. Compounds 9 and 18 showed the most selective effects against human neutrophil elastase release, with IC50 values of 0.8 ± 0.1 and 1.7 ± 0.6 μM, respectively, and were 130-fold more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in this anti-inflammatory assay. These two compounds could be developed as new lead anti-inflammatory agents.

Graphical abstractTwenty-six Fmoc-based dipeptides were designed and synthesized. Among them, compounds 9 and 18 showed potent inhibitory effect on human neutrophils elastase release, with IC50 values of 0.8 ± 0.1 and 1.7 ± 0.6 μM, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide