Novel carbonothioate from <i>Paecilomyces subglobosus</i> CBK3: antibacterial and anticancer <i>in vitro</i> and <i>in silico</i> study

A novel organosulfur compound, <i>O</i>-(4-aminophenethyl) <i>S</i>-methyl carbonothioate (OAPC), was isolated from <i>Paecilomyces subglobosus</i>, an endophytic fungus from tree ferns. Although it showed no notable antibacterial activity, OAPC exhibited moderate cytotoxicity against MCF-7 breast cancer cells (IC₅₀ = 416.87 ± 25.79 µg/mL). Molecular docking revealed favourable binding to oestrogen receptor alpha (ER-α) with -5.82 kcal/mol, close to paclitaxel (-6.55 kcal/mol), while having lower affinity for HER2. Molecular dynamics confirmed the stability of the OAPC-ER-α complex over 100 ns. ADMET predictions suggest good intestinal absorption (90.44%) but poor skin permeability and limited tissue distribution. OAPC is unlikely to cross the blood-brain barrier (BBB) or impact the central nervous system (CNS) but may inhibit CYP1A2 and has low systemic clearance. Toxicity profiling indicates potential hepatotoxicity and mutagenicity. Despite safety concerns, OAPC shows promise as an ER-α-targeting anticancer lead compound, warranting further optimisation and toxicological evaluation.