Bioactive Naphtho-α-Pyranones from Two Endophytic Fungi of the Genus Polyphilus

In the course of our survey to study the metabolic potential of two species of a new helotialean genus Polyphilus , namely P. frankenii and P. sieberi , their crude extracts were obtained using different cultivation techniques, which led to the isolation and characterization of two new naphtho- α -pyranone derivatives recognized as a monomer ( 1 ) and its 6,6′-homodimer ( 2 ) together with two known diketopiperazine congeners, outovirin B ( 3 ) and (3 S ,6 S )-3,6-dibenzylpiperazine-2,5-dione ( 4 ). The structures of isolated compounds were determined based on extensive 1D and 2D NMR and HRESIMS. The absolute configuration of new naphtho- α -pyranones was determined using a comparison of their experimental ECD spectra with those of related structural analogues. 6,6′-binaphtho- α -pyranone talaroderxine C ( 2 ) exhibited potent cytotoxic activity against different mammalian cell lines with IC 50 values in the low micromolar to nanomolar range. In addition, talaroderxine C unveiled stronger antimicrobial activity against Bacillus subtilis rather than Staphylococcus aureus with MIC values of 0.52 µg mL −1 (0.83 µM) compared to 66.6 µg mL −1 (105.70 µM), respectively.