LC-MS/MS-guided discovery of japonamides C and D, two new cyclohexadepsipeptides, from the -derived endophytic fungus TE-739D.

Endophytic fungi belonging to the genus have received substantial attention due to their notable secondary metabolic potential. In this study, chemical investigations using LC-MS/MS-based molecular networking on the endophytic fungus TE-739D led to the discovery of two new cyclohexadepsipeptides, namely japonamides C () and D (), along with three known cyclodipeptides (-). Their structures, including the absolute configurations of the amino acid residues, were elucidated through spectroscopic data analysis and an optimized Marfey's method. The newly discovered compounds, japonamides C () and D (), were screened for broad-spectrum cell proliferation inhibitory activity against 20 different human cell lines. The results indicated that both compounds displayed broad-spectrum antiproliferative activity against MKN-45, HCT116, TE-1, 5,637, CAL-62, and A-637 cells, with inhibition rates ranging from 55.0 to 72.3%. Moreover, the antibacterial activity of compounds - against two Gram-positive bacteria and two Gram-negative bacteria was also evaluated.