Abstract
A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated.
Original language | English |
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Article number | 253 |
Journal | Marine Drugs |
Volume | 15 |
Issue number | 8 |
ISSN | 1660-3397 |
DOIs | |
Publication status | Published - Aug 2017 |
Externally published | Yes |
Bibliographical note
Funding Information:Acknowledgments: Funding is acknowledged from PharmaSea (Grant Agreement No 312184). Thanks to Lisette Knoth-Nielsen for assistance with media and crude extracts. We thank the NMR center • DTU and the Villum foundation for 800 MHz NMR time. We are grateful to Agilent Technologies for the Thought Leader Donation of the UHPLC-QTOF system.
Keywords
- Antifungal
- Bioguided-discovery
- Cytotoxicity
- Dereplication
- Ilicicolin H
- Marine-derived
- MS/HRMS
- Pimarane-type diterpenoids