Omnipolyphilins A and B: Chlorinated Cyclotetrapeptides and Naphtho-α-pyranones from the Plant Nematode-Derived Fungus <i>Polyphilus sieberi</i>

Abstract

Chemical exploration for two isolates of the recently described ascomycete species <i>Polyphilus</i> <i>sieberi</i>, derived from the eggs of the plant parasitic nematode <i>Heterodera filipjevi</i>, afforded the identification of many compounds that belong to various metabolite families: two previously undescribed chlorinated cyclotetrapeptides, omnipolyphilins A (<b>1</b>) and B (<b>2</b>), one new pyranonaphthoquinone, ventiloquinone P (<b>3</b>), a 6,6'-binaphto-α-pyranone dimer, talaroderxine D (<b>4</b>) in addition to nine known metabolites (<b>5</b>-<b>13</b>) were isolated from this biocontrol candidate. All isolated compounds were characterized by comprehensive 1D, 2D NMR, and HR-ESI-MS analyses. The absolute configurations of the cyclotetrapeptides were determined by a combination of advanced Marfey's method, ROE correlation aided by conformational analysis, and TDDFT-ECD calculations, while ECD calculations, Mosher's method, and experimental ECD spectra were used for ventiloquinone P (<b>3</b>) and talaroderxine D (<b>4</b>). Among the isolated compounds, talaroderxine D (<b>4</b>) showed potent antimicrobial activities against <i>Bacillus subtilis</i> and <i>Staphylococcus aureus</i> with MIC values of 2.1 and 8.3 μg mL^-1, respectively. Additionally, promising inhibitory effects on talaroderxine D (<b>4</b>) against the formation of <i>S. aureus</i> biofilms were observed up to a concentration of 0.25 μg mL^-1. Moreover, ophiocordylongiiside A (<b>10</b>) showed activity against the free-living nematode <i>Caenorhabditis elegans</i>.