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 IC(50) values of 0.8+/-0.1 and 1.7+/-0.6muM, 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.
Yen
Chiao-Ting
CT
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Hwang
Tsong-Long
TL
Wu
Yang-Chang
YC
Hsieh
Pei-Wen
PW
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010196:Pancreatic Elastase / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004151:Dipeptides; D013481:Superoxides; C011670:N-benzoylphenylalanylphenylalinol acetate; D010196:Pancreatic Elastase