Bioactive Naphtho-α-Pyranones from Two Endophytic Fungi of the Genus IPolyphilus/I

• Published in: Antibiotics (Basel) 2023-08, Vol.12 (8)
• Main Authors: Wennrich, Jan-Peer, Sepanian, Ellen, Ebada, Sherif S, Llanos-Lopez, Natalia A, Ashrafi, Samad, Maier, Wolfgang, Kurtán, Tibor, Stadler, Marc
• Format: Article
• Language: English
• Subjects: Fungi; Metabolites; Oxytetracycline
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12081273

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 (3S,6S)-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[sub.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[sup.−1] (0.83 µM) compared to 66.6 µg mL[sup.−1] (105.70 µM), respectively.