Deep-sea-derived fungi have emerged as a prolific source of structurally novel and pharmacologically active secondary metabolites, representing an invaluable reservoir of lead compounds for drug discovery and development. In the present study, one new tyramine derivative (1) and 28 known compounds (2-29) were obtained from Talaromyces wortmannii MCCC 3A01136, a fungus isolated from the intestinal contents of a stranded deep-sea whale (Mesoplodon densirostris) in the East China Sea. The structures were elucidated via comprehensive analysis of 1D and 2D NMR data, HRESIMS, NMR computations coupled with DP4+ probability analysis, and ECD calculations. Comazaphilones E (2) and C (6) significantly inhibited renin-angiotensin system-selective lethal 3 (RSL3)-induced ferroptosis with a half maximal effective concentration (EC50) value of 4.52 and 13.73 µM, respectively.
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