Oxalicpyridones A-D, 2-pyridone alkaloids from a marine-derived fungus Penicillium oxalicum suppressing proliferation and metastasis against small cell lung cancer.

To explore bioactive specialized metabolites from marine-derived fungi, four previously undescribed 2-pyridone alkaloids, oxalicpyridones A-D (1-4), two unreported tetramic acids, tolypocladenols G and H (5 and 6), together with five known 2-pyridone derivatives (7-11), were isolated from the marine-derived fungus Penicillium oxalicum SCSIO 41320. Their structures, including absolute configurations, were elucidated by extensive nuclear magnetic resonance (NMR) spectroscopic analysis, X-ray single-crystal diffraction, and calculations of electronic circular dichroism (ECD), 13C NMR, and optical rotation (OR). Additionally, oxalicpyridones A-C (1-3) inhibited the viability of several small-cell lung cancer (SCLC) cell lines in a dose-dependent manner. Among them, oxalicpyridone A (1) not only inhibited proliferation, induced apoptosis, and suppressed metastasis of SCLC cells in vitro, but also significantly inhibited the growth of SCLC cell-derived xenograft tumors in zebrafish in vivo. Collectively, these findings enrich the chemical diversity of marine-derived 2-pyridone alkaloids and provide potential lead compounds for anticancer drug discovery.