Ultraperformance liquid chromatography-based metabolite profiling and cytotoxic activity of the ethyl acetate extract of two endophytic Penicillium sp.

The present study evaluated the mycochemical abundance, and the cytotoxic and hemolytic activities of ethyl acetate extract (EAE) of endophytic Penicillium camponotum (PC) and Penicillium fuscoglaucum (PF). Higher yield was noted in EAE-PF with total phenols (26.59 ± 1.52 mg of GAE/g DW) and flavonoids (3.12 ± 1.83 mg of QE/g DW). The EAE-PF inhibited the proliferation of two breast cancer cells (BT-474 and MDA-MB-231) with the half-maximal inhibitory concentration (IC50) of 0.112 and 0.120 mg/mL, respectively, while the IC50 values against HEK-293 and NIH3T3 cells were not found up to 1 mg/mL dose of EAE-PF. Moreover, EAE-PF (1 mg/mL) demonstrated its trivial toxicity in erythrocytes with ∼4.6% of hemolysis. The metabolic profiling of EAE-PF revealed the presence of mycochemicals including penicitide B (C18H34O5), p-hydroxyphenethyl anisate (C16H16O4), and dihydroxystearic acid (C18H36O4). Furthermore, these compounds exhibited substantial interactions with human cancer-related proteins such as epidermal growth factor receptor (EGFR), N-myristoyltransferase isoform 2 (NMT-2), cyclin-dependent kinase 2 (CDK-2), and c-mesenchymal epithelial transition factor kinase (c-Met K) evidenced by in-silico molecular docking analysis. Overall, this report suggests further studies on the isolation and purification of novel anti-cancer compounds from endophytic PF.