Anti‐Proliferative and Antioxidant Potential of Podophyllotoxin From the Endophytic Fungus Dactylonectria torresensis

ABSTRACT The study investigated Dactylonectria torresensis as a sustainable source of podophyllotoxin (PTOX), a key precursor for anticancer drugs such as etoposide and teniposide. The fungus was identified through morphological analysis and ITS rDNA sequencing. PTOX from the fungal extract was isolated and characterized using high‐performance liquid chromatography, high‐resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. Antioxidant activity was evaluated via 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and reducing power assays, showing comparable 50% inhibition (IC 50 ) values for standard and fungal PTOX – 297.4 versus 309.8 µg/mL (DPPH) and 306.6 versus 316.3 µg/mL (reducing power). Cytotoxicity against MCF‐7 breast cancer cells also revealed similar IC 50 values: 3.083 µM for standard and 3.188 µM for fungal PTOX. PTOX production was optimized through a two‐phase statistical approach: Plackett‐Burman Design followed by Face‐Centered Central Composite Design. Initially, D. torresensis produced 78.46 µg/g dry weight (DW) of PTOX, which increased 6.35‐fold to 498.76 µg/g DW after optimization.