Secondary Metabolites of the Marine Sponge-Derived Fungus 1901NT-1.40.2 and Their Antimicrobial and Anticancer Activities.

The aim of this study was to investigate the metabolites in 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane triterpenoid aspersubrin A () and pyrazine alkaloid ochramide E () were established using NMR and HR ESI-MS. The absolute configuration of was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide () and sclerin (); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (); the bis-indolyl benzenoid alkaloids kumbicin D (), asterriquinol D dimethyl ether (), petromurin C (); and the cyclopentenedione asterredione () were isolated. The effects of compounds - on the growth and biofilm formation of the yeast-like fungus and the bacteria and were investigated. Compounds and inhibited growth and biofilm formation at an IC of 7-10 µM. Moreover, the effects of compounds - on non-cancerous H9c2 cardiomyocytes, HaCaT keratinocytes, MCF-10A breast epithelial cells, and breast cancer MCF-7 and MDA-MB-231 cells were also investigated. Compound (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, significantly decreased the area of MCF-7 3D spheroids by approximately 30%. A competitive test with 4-hydroxytamoxyfen and molecular docking showed that estrogen receptors (ERβ more than ERα) were involved in the anticancer effect of petromurin C ().