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

The aim of this study was to investigate the metabolites in <i>Aspergillus subramanianii</i> 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 (<b>1</b>) and pyrazine alkaloid ochramide E (<b>2</b>) were established using NMR and HR ESI-MS. The absolute configuration of <b>1</b> was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide (<b>3</b>) and sclerin (<b>4</b>); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (<b>5</b>); the bis-indolyl benzenoid alkaloids kumbicin D (<b>6</b>), asterriquinol D dimethyl ether (<b>7</b>), petromurin C (<b>8</b>); and the cyclopentenedione asterredione (<b>9</b>) were isolated. The effects of compounds <b>3</b>-<b>9</b> on the growth and biofilm formation of the yeast-like fungus <i>Candida albicans</i> and the bacteria <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> were investigated. Compounds <b>5</b> and <b>6</b> inhibited <i>C. albicans</i> growth and biofilm formation at an IC₅₀ of 7-10 µM. Moreover, the effects of compounds <b>3</b>-<b>9</b> 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 <b>8</b> (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, <b>8</b> 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 (<b>8</b>).