Pyrrolyl 4-quinolone alkaloids from the mangrove endophytic fungus Penicillium steckii SCSIO 41025: Chiral resolution, configurational assignment, and enzyme inhibitory activities

Abstract

Six undescribed 4-quinolone alkaloids, including four racemic mixtures, (±)-oxypenicinolines A-D, and two related ones, penicinolines F and G, together with seven known analogues, were isolated from the mangrove-derived fungus Penicillium steckii SCSIO 41025 (Trichocomaceae). The racemates were separated by HPLC using chiral columns. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) experiments, and single-crystal X-ray diffraction analysis. Structurally, (±)-oxypenicinolines A-D shared with an unusual 6/6/5/5 tetracyclic system incorporating a rare tetrahydro-pyrrolyl moiety. A plausible biosynthetic pathway for pyrrolyl 4-quinolone alkaloids is proposed. (±)-oxypenicinoline A and quinolactacide displayed α-glucosidase inhibitory activity with the IC₅₀ values of 317.8 and 365.9 μΜ, respectively, which were more potent than that of acarbose (461.0 μM). Additionally, penicinoline and penicinoline E showed weak inhibitions toward acetylcholinesterase (AChE).

Keywords: Acanthaceae; Alkaloids; Avicennia marina (Forsk.) vierh.; Enantiomers; Enzyme inhibitory activity; Mangrove endophytic fungus; Penicillium steckii; Trichocomaceae.