Abstract: Tyrosyl-DNA phosphodiesterase 1 (TDP1) is currently recognized as a potential target for cancer treatment. However, no related drugs have been marketed or reported in clinical research. In order to discover potential TDP1 inhibitors, the soft coral-associated symbiotic and epiphytic fungi Aspergillus terreus EGF7-0-1 were fermented with rice media. The secondary metabolites were isolated with the various chromatography technologies (such as TLC, CC, HPLC, etc.) to afford eight γ-aromatic butenolide lignans. Based on NMR, HR-ESI-MS, OR and compare with the literature, their structures were determined as butyrolactones I~V (1~5), aspernolide E (6), asperteretal D (7) and terrusnolide A (8). In this study, the inhibitory activity of these compounds against tyrosyl -DNA phosphodiesterase 1 (TDP1) in vitro was studied for the first time, but it was unfortunate that compounds 1~8 did not show any inhibitory abilities against TDP1. This study provides theoretical data for the discovery of TDP1 inhibitors.

Key words: traditional marine Chinese medicine soft coral, Aspergillus terreus, γ-aromatic butenolides lignans, structural identification, TDP1 inhibitors