New natural products from Aspergillus candidus NRRL 5214 and their glycosylation by Streptomyces chromofuscus ATCC 49982

Fungi represent a rich source of bioactive natural products. In this study, we present the isolation and identification of two new diphenyl ethers, named aspergilluscandidus A (1) and aspergilluscandidus B (2), along with a known compound terphenyllin (3), from the fungal strain Aspergillus candidus NRRL 5214. The chemical structures of compounds 1–3 were characterized through extensive 1D and 2D NMR analysis. Compounds 1 and 3 were subsequently biotransformed into two new glycosides, namely aspergilluscandidus C (4) and terphenyllin-4″-O-β-d-glucuronide (5) by the actinomycete strain Streptomyces chromofuscus ATCC 49982. The cytotoxicity assay revealed that the glycosylated products 4 and 5 exhibited significantly improved activity against the glioblastoma 33 cell line compared to their respective substrates, decreasing the IC₅₀ from 8.15 ± 1.09 μM (1) to 5.41 ± 0.30 μM (4) and from 88.29 ± 10.54 μM (3) to 31.25 ± 4.20 μM (5), respectively. Our study emphasizes A. candidus NRRL 5214 as a promising source of new natural products and presents an effective strategy for modifying both diphenyl ether and p-terphenyl compounds using S. chromofuscus ATCC 49982 to enhance their cytotoxicity activity.