Chimeric Pyridone Alkaloids from the Mangrove Endophytic Fungus Aspergillus niger

Abstract

Thirty-four chimeric pyridone alkaloids, including twenty-eight new compounds named aspernigrins F₁−F₈, G₁−G₅, H₁−H₇, and I−P (1−28), were isolated from the mangrove endophytic fungus Aspergillus niger H6a, together with six known ones (29−34). The structures of these compounds were elucidated by HRESIMS, NMR spectroscopic data, single-crystal X-ray diffraction analyses, TDDFT-ECD calculations, and chemical methods, including Marfey’s derivatization. The structure of 26 contains two units of 2-aminododecanoic acid, whereas those of 27 and 28 not only contain two moieties of 2-aminododecanoic acid but also possess an ester-linked neo-inositol group, featuring unprecedented chimeric pyridone alkaloids with amphiphilic properties. Compound 26 exhibited antibacterial activity against Enterococcus faecalis and Micrococcus luteus with minimum inhibitory concentration values of 8.0 and 16.0 μg/mL, respectively, whereas compound 27 displayed anti-tumor activity against the Hela cell line with an IC₅₀ value of 15.9 μM. Further studies disclosed that 27 exerted concentration-dependent anti-tumor activity against HeLa cells, including the inhibition of cell proliferation, invasion, and migration, along with the successful induction of mitochondrial-mediated cell apoptosis and the arrest of cell cycle in the G₀/G₁ phase. This work provides insight into the discovery of new pyridone alkaloids as lead compounds for the development of anti-bacterial and anti-tumor agents.