Fumigaclavines K−M, undescribed ergot alkaloids from the mangrove-derived fungus Aspergillus sp. DVXT-221 with cytotoxic and NO inhibitory activities

Abstract

Chemical investigation of the mangrove-derived fungus Aspergillus sp. DVXT-221 led to isolation of three undescribed ergot alkaloids, fumigaclavines K−M (1, 2, and 4), and seven known compounds, fumigaclavines I (3), C (5), and E (6), monomethylsulochrin (7), 8′-O-methylasterric acid (8), 2,3′-dimethylosoate (9), and chaetominine (10). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and HRESI mass spectra. The absolute configurations of 1, 2, and 4 were clarified by time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) spectroscopic analyses. Compound 2 contained the first example of N-methyl oxide among the previously reported ergot alkaloids. Compounds 1 and 3 showed weak cytotoxicity on both HepG2 and MCF7 cell lines, with IC₅₀ values ranging from 61.1 ± 3.1 to 77.2 ± 1.5 μM. Compounds 1 and 9 exhibited stronger inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW264.7 cells, with IC₅₀ values of 5.3 ± 0.2 and 8.7 ± 0.4 μM, respectively, whereas weaker NO inhibitory effects were observed for 2–4, 8, and 10, with IC₅₀ values ranging from 20.5 ± 0.8 to 36.1 ± 2.3 μM. Both 1 and 9 were suggested to inhibit NO overproduction via down-regulating the action of iNOS protein by molecular docking simulations.