neo-Dicitrinols A–C: Unprecedented PKS-NRPS hybrid citrinin dimers with ferroptosis inhibitory activity from the deep-sea-derived Penicillium citrinum W22

The chemical investigation into the EtOAc extract of the deep-sea-derived fungus Penicillium citrinum W22 yielded three unprecedented citrinin dimers, neo-dicitrinols A–C (1–3) and a known one, penicitrinone A (4). Their structures were elucidated by extensive analysis of spectroscopic data, electronic circular dichroism (ECD) calculation, X-ray diffraction, and biogenetic consideration. neo-Dicitrinols A–C (1–3), bearing a tetramic acid unit, represent the first example of citrinin analogues as hybrid polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) products. neo-Dicitrinol C (3) significantly inhibited renin-angiotensin system-selective lethal 3 (RSL3)-induced ferroptosis with a half maximal effective concentration (EC50) value of 21.6 μmol/L.