AUTHOR=Gao Zhong-Jie , Cao Lu-Lu , Ren Hai-Ping , Yu Hua , Wang Yan 

TITLE=Novel chlorinated and nitrogenated azaphilones with cytotoxic activities from the marine algal-derived fungus Chaetomium globosum 2020HZ23

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1252563

DOI=10.3389/fmicb.2023.1252563

ISSN=1664-302X

ABSTRACT=<p>Two novel chlorinated and nitrogenated azaphilones, namely <italic>N</italic>-butyl-2-aza-2-deoxychaetoviridin A (<bold>1</bold>) and <italic>N</italic>-hexyl-2-aza-2-deoxychaetoviridin A (<bold>2</bold>), along with a previously identified analogue, chaetoviridin A (<bold>3</bold>), were successfully obtained from <italic>Chaetomium globosum</italic> 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 <italic>in vitro</italic> cytotoxicity evaluation toward the A549 cancer cell line. Both compounds <bold>1</bold> and <bold>2</bold> demonstrated significant cytotoxicity, as evidenced by their respective IC<sub>50</sub> values of 13.6 and 17.5 μM. Furthermore, <bold>1</bold> and <bold>2</bold> demonstrated potent cell migration inhibition, which elevated with increasing dose concentration. In contrast, compound <bold>3</bold> exhibited less cytotoxic activity relative to <bold>1</bold> and <bold>2</bold>, 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.</p>