New Hybrid Phenalenone Dimer, Highly Conjugated Dihydroxylated C28 Steroid and Azaphilone from the Culture Extract of a Marine Sponge-Associated Fungus, Talaromyces pinophilus KUFA 1767

• Published in: Marine drugs Vol. 21; no. 3; p. 194
• Main Authors: Machado, Fátima P., Rodrigues, Inês C., Georgopolou, Aikaterini, Gales, Luís, Pereira, José A., Costa, Paulo M., Mistry, Sharad, Hafez Ghoran, Salar, Silva, Artur M. S., Dethoup, Tida, Sousa, Emília, Kijjoa, Anake
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 21.03.2023; MDPI
• Subjects: Absolute configuration; Acetates; Acetic acid; Antibacterial activity; Antibiotic resistance; Antibiotics; azaphilone; Biofilms; Carbon; Configurations; Crystallography; Dimers; E coli; Enterococcus faecalis; Escherichia coli; Ethyl acetate; Fungi; highly conjugated C28 steroid; hybrid oxyphenalenone; Marine invertebrates; marine sponge-associated fungus; Metabolites; Methicillin; Multidrug resistance; NMR; Nuclear magnetic resonance; Pseudomonas aeruginosa; Staphylococcus aureus; Talaromyces; Talaromyces pinophilus; Trichocomaceae; Vancomycin; β Lactamase
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md21030194

An undescribed hybrid phenalenone dimer, talaropinophilone (3), an unreported azaphilone, 7-epi-pinazaphilone B (4), an unreported phthalide dimer, talaropinophilide (6), and an undescribed 9R,15S-dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one (7) were isolated together with the previously reported bacillisporins A (1) and B (2), an azaphilone derivative, Sch 1385568 (5), 1-deoxyrubralactone (8), acetylquestinol (9), piniterpenoid D (10) and 3,5-dihydroxy-4-methylphthalaldehydic acid (11) from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Talaromyces pinophilus KUFA 1767. The structures of the undescribed compounds were elucidated by 1D and 2D NMR as well as high-resolution mass spectral analyses. The absolute configuration of C-9′ of 1 and 2 was revised to be 9′S using the coupling constant value between C-8′ and C-9′ and was confirmed by ROESY correlations in the case of 2. The absolute configurations of the stereogenic carbons in 7 and 8 were established by X-ray crystallographic analysis. Compounds 1,2, 4–8, 10 and 11 were tested for antibacterial activity against four reference strains, viz. two Gram-positive (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains, viz. an extended-spectrum β-lactamase (ESBL)-producing E. coli, a methicillin-resistant S. aureus (MRSA) and a vancomycin-resistant E. faecalis (VRE). However, only 1 and 2 exhibited significant antibacterial activity against both S. aureus ATCC 29213 and MRSA. Moreover, 1 and 2 also significantly inhibited biofilm formation in S. aureus ATCC 29213 at both MIC and 2xMIC concentrations.