Abstract
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 ICfrom 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.
Overview
- The study isolated and identified two new diphenyl ether compounds, aspergilluscandidus A (1) and aspergilluscandidus B (2), from the fungal strain Aspergillus candidus NRRL 5214.
- The compounds were characterized through extensive 1D and 2D NMR analysis and biotransformed into new glycosides by the actinomycete strain Streptomyces chromofuscus ATCC 49982.
- The study aimed to investigate the cytotoxicity activity of the compounds against the glioblastoma 33 cell line and explore a novel strategy for modifying diphenyl ether and p-terphenyl compounds using S. chromofuscus ATCC 49982.
Comparative Analysis & Findings
- Compounds 1 and 3 were biotransformed into new glycosides, aspergilluscandidus C (4) and terphenyllin-4″-O-β-d-glucuronide (5), respectively, which exhibited improved cytotoxicity activity against the glioblastoma 33 cell line compared to their respective substrates.
- The IC50 of glycosylated products 4 and 5 was significantly lower than that of compounds 1 and 3, respectively, indicating enhanced cytotoxicity activity.
- The study demonstrates that biotransformation can be an effective strategy for modifying diphenyl ether and p-terphenyl compounds to improve their cytotoxicity activity.
Implications and Future Directions
- The study highlights Aspergillus candidus NRRL 5214 as a promising source of new natural products and provides a new strategy for modifying diphenyl ether and p-terphenyl compounds.
- Future studies can explore the potential of biotransformation to improve the cytotoxicity activity of other natural compounds and expand the range of bioactive molecules derived from fungi.
- Elucidating the mechanisms of biotransformation and its effects on the structural and biological properties of the compounds will be crucial for the development of more effective and targeted therapies.