Novel chlorinated and nitrogenated azaphilones with cytotoxic activities from the marine algal-derived fungus 2020HZ23.

Two novel chlorinated and nitrogenated azaphilones, namely -butyl-2-aza-2-deoxychaetoviridin A () and -hexyl-2-aza-2-deoxychaetoviridin A (), along with a previously identified analogue, chaetoviridin A (), were successfully obtained from 2020HZ23, a marine algal-sourced endophytic fungus. The planar structures as well as the absolute configurations of these new metabolites were determined utilizing a synergistic approach that involved both spectroscopic techniques (1D/2D NMR and HRESIMS) and Density Functional Theory (DFT) calculations. Each compound was subject to cytotoxicity evaluation toward the A549 cancer cell line. Both compounds and demonstrated significant cytotoxicity, as evidenced by their respective IC values of 13.6 and 17.5 μM. Furthermore, and demonstrated potent cell migration inhibition, which elevated with increasing dose concentration. In contrast, compound exhibited less cytotoxic activity relative to and , suggesting that the cytotoxic potency escalates with N-substitution at the C-2 position and the introduction of a side chain. This finding could offer implications for future studies aimed at designing and refining lead compounds within this class.