Cytotoxic metabolites from the endophytic fungus Penicillium sp. ArD1 derived from Corchorus olitorius seeds

Corchorus olitorius L. seeds are a rich source of endophytic fungi, which afford many cytotoxic secondary metabolites. The fungus was taxonomically identified via sequencing as Penicillium sp. ArD1 (closely related to P. oxalicum ). The fungal extract was subjected to chromatographic separation, leading to the isolation and structural elucidation of four compounds: two naphtho-pyrones (( 1 ) and ( 2 )), the cyclic pentapeptide malformin A1 ( 3 ), and the fatty acid Tridecanoic acid ( 4 ). Structures were confirmed using extensive 1D and 2D NMR as well as mass spectrometry. The isolated metabolites were evaluated for cytotoxicity against human lung carcinoma cell lines A549 and H1299. malformin A1 (3) demonstrated the highest and most potent activity, yielding IC ₅₀ values of 0.75 ± 0.02 and 0.85 ± 0.14 µM, respectively. In addition, malformin A1 revealed different hydrogen bonding and hydrophobic interactions within the enzyme’s active site of matrix metalloproteinase-9 (MMP-9) in the molecular docking study. These findings highlight malformin A1 from endophytic Penicillium sp. as a promising and highly potent lead compound for the development of anti-lung cancer therapeutics.