Cytotoxic N-alkylated pyrroles from the endophytic fungus Penicillium oxalicum

Endophytic microorganisms colonizing plant tissues synthesize diverse secondary metabolites within their unique ecological niche, many of which possess promising pharmacological properties and represent a rich repository of bioactive molecules. During our ongoing investigation of plant-derived endophyte for novel bioactive compounds, two previously unreported N-alkylated pyrroles (1-2), along with six meroterpenoids (3-8), one sesquiterpene (9), three lactones (10-12), three sterols (13-15), and two diterpenoids (16-17) were isolated from Penicillium oxalicum strain obtained from Cedrus spp. Their structures were elucidated through comprehensive spectroscopic analyses (NMR and HRESIMS). Although pyrrole alkaloids are widespread in nature, N-alkylated pyrrole derivatives remain relatively rare, and their biological activities are poorly characterized. In this study, compounds 1 and 2 demonstrated the most potent activities against A549 cell with the IC₅₀ value of 7.86 ± 0.81 and 9.37 ± 0.42 μM, respectively. Additionally, compound 1 showed weak antibacterial activity against Staphylococcus aureus in agar diffusion assay.