ABSTRACT
Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages.
Subject(s)
Alkaloids , Interleukin-6 , Lactams , Porifera , Pyrroles , Animals , Mice , Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Porifera/chemistry , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , RAW 264.7 Cells , Lactams/chemistry , Lactams/pharmacology , Lactams/isolation & purification , Pyrroles/pharmacology , Pyrroles/chemistry , Pyrroles/isolation & purification , China , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Molecular Structure , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Structure-Activity Relationship , Macrophages/drug effects , Macrophages/metabolism , Dose-Response Relationship, DrugABSTRACT
Chemical investigation of the EtOH extract of the sponge Axinella sp. collected from the South China Sea resulted in the identification of one new pyrrololactam alkaloid, axinellamine E (2), along with four known analogs (1, 3-5). Compound 1 was initially separated as enantiomers and was further separated to be optically pure compounds (1 a and 1 b) by a chiral column. The planar structure of compound 2 was determined mainly by 1D-, 2D-NMR, and HR-ESI-MS data analyses. Absolute configurations of 1 a and 1 b was defined by calculated ECD spectra method. All of the compounds were evaluated for their anti-inflammatory activities against nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells among which compound 1 showed weak activity at 40 µg/mL. Plausible biosynthetic pathways corresponding to aldisine analogs of 1, 2, 4, and 5 were also discussed.