Sch-351633

Four new sesquiterpenes ( 1–4 ) and 34 known compounds ( 5–38 ) were isolated from the deep‐sea‐derived fungus Tritirachium oryzae . The structures of the new compounds were established by detailed analyses of the nuclear magnetic resonance (NMR), mass spectrometry (MS), optical rotatory dispersion (ORD), and electronic circular dichroism (ECD) data. An in vitro antifungal experiment was conducted against Phytophthora nicotianae , and compound 7 exhibited prominent inhibitory activity with an EC 50 value (5 days) of 18.189 µg/mL, surpassing the commercially available fungicide pyrimethanil. Further mechanism studies showed that compound 7 treatment disrupted hyphal morphology and increased membrane permeability in P. nicotianae , resulting in wrinkled and twisted mycelium, increased conductivity, and elevated malondialdehyde (MDA) content. With the increasing concentration of compound 7 , succinate dehydrogenase (SDH) and NAD–malate dehydrogenase (NAD–MDH) enzyme activities gradually decreased, ultimately leading to the blockage of the tricarboxylic acid (TCA) cycle. In addition, compound 7 affected the activities of antioxidant enzymes in a concentration‐ and time‐dependent manner, generally leading to a decrease in superoxide dismutase (SOD) and catalase (CAT) activities and fluctuations in peroxidase (POD) and phenylalanine ammonia lyase (PAL) activity. In conclusion, the present study revealed that naturally occurring terpenoids from marine T. oryzae could be used as novel anti– P. nicotianae molecules by blocking the TCA cycle, indicating the potential to develop agrochemical fungicides for tobacco protection.

Five previously undescribed phenylpyridones, designated as citridones H-L (1-5), along with seven known compounds, were characterized from the rice medium culture of the Cineraria repanda-derived endophytic fungus Penicillium oxalicum. Their structures were elucidated through detailed interpretation of UV, NMR, and HR-ESI-MS data. The absolute configurations of C-2 and C-3 in compounds 1-4 were determined by spectroscopic analysis and ECD calculations, while the C-5' configurations were established through computational ¹³C NMR and DP4+ analyses. These compounds represent a novel scaffold of chromone-phenylpyridone hybrids, making only the second report of such compounds from the Penicillium genus and the first to feature a unique (E)-5-methylhepta-1,3-diene group at the C-2 position. Additionally, a biosynthetic pathway for these novel chromone-phenylpyridones is proposed for the first time. Notably, compounds 3 and 4 exhibited cytotoxicity against HCT116 and H1299 cell lines when used in combination, with IC₅₀ values of 4.15 ± 0.34 and 9.07 ± 1.64 μM, respectively. Furthermore, compounds 3, 4 and 5 demonstrated significant inhibitory effects against Staphylococcus aureus, with MIC values of 64, 64 and 8 μg/mL, respectively.