%0 Journal Article %T Penisimplicins A and B: Novel Polyketide-Peptide Hybrid Alkaloids from the Fungus Penicillium simplicissimum JXCC5. %A Wang QY %A Gao Y %A Yao JN %A Zhou L %A Chen HP %A Liu JK %J Molecules %V 29 %N 3 %D 2024 Jan 27 %M 38338359 %F 4.927 %R 10.3390/molecules29030613 %X In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 μM.