A cyclic lipodepsipeptide, a spirolactone, and a chromanone from the marine fungus Verruculina enalia (Kohlm.) Kohlm. & Volkm.-Kohlm. BCC 22226
Introduction
Marine fungi in the order Pleosporales have been documented as an important source of diverse secondary metabolites with a broad range of biological activities [1]. These include an antimalarial and anticancer 14-membered resorcyclic macrolide (aigialomycin D) from Aigialus parvus BCC 5311 [2], an antimalarial tetronic acid (nodulisporacid A) from Nodulisporium sp. CRIF1 [3], an antibiotic polyketide (lindgomycin) from the Lindgomycetaceae strain KF970 [4], and an antifungal azaphilone (pleosporalone A) from the Pleosporales sp. fungus CF09-01 [5]. Verruculina is a monotypic genus within the order Pleosporales. It contains only a single species, Verruculina enalia, and has been well recognized as an obligate marine fungus. Even being one of the frequently encountered fungi in the mangroves [6,7], secondary metabolites produced from this fungal genus have been scarcely reported. To the best of our knowledge, only a new coumaranone, (enalin A, 8), a new α-diketone (enalin B) together with a known furfural and three known diketopiperazines were previously described from V. enalia, isolated from decayed wood of Cassurina tree from a salt lake [8]. As part of our ongoing research on novel bioactive compounds from Thai marine fungi, the crude extract of V. enalia BCC 22226, isolated from driftwood collected from the beach in Phetchaburi province, Thailand, showed antibacterial activity against Bacillus cereus with a MIC value of 50 μg/mL. Further study of the large scale culture under submerged liquid fermentation conditions led to the isolation and structure elucidation of a cyclic lipodepsipeptide [verruculin (1)], a rosigenin and an aposphaerin analogues [verruculinone (2) and 7-O-methylaposphaerin C (4)], together with six known compounds including rosigenin (3) [9], aposphaerin C (5) [10], (−)-cercosporamide (6) [11,12], (−)-usnic acid (7) [12,13], enalin A (8) [8], and 2,6-dihydroxy-3-methyl-4-methoxyacetophenone (9) [14] (Fig. 1).
Section snippets
Results and discussion
Compounds 1, 5–7, and 9 were obtained from mycelial extract after purification by Sephadex LH-20 column chromatography and reversed phase HPLC. The crude EtOAc extract of the culture filtrate was fractionated by a combination of Sephadex LH-20, and silica gel column to give 2. Compounds 3, 4 and 8 were obtained after further purification by reversed phase HPLC.
Compound 1 was identified as having a molecular formula of C47H66N8O11 as deduced from the sodium adduct in the HR-ESI-TOF (m/z 941.4740
Conclusion
In this study, diverse chemical structures including a cyclic lipodepsipeptide (1), a rosigenin and an aposphaerin analogues (2 and 4), together with six known compounds (3, 5, and 6–9) were isolated from the marine fungus Verruculina enalia BCC 22226. Verruculin (1) showed weak anti-TB and antibacterial (against B. cereus) activities (MIC values = 50 and 25 μg/mL, respectively), while verruculinone (2) displayed cancer cell line (MCF-7 and NCI–H187) cytotoxicity (with respective IC50 values of
General
Optical rotations were determined using JASCO P-1030 and P-2000 digital polarimeters. CD spectra were measured using a JASCO J-810 spectropolarimeter. IR spectra were taken on a Bruker VECTOR 22 spectrometer. NMR spectra were taken on Bruker DRX 400 and Bruker AV500D spectrometers. HR-ESI-TOF mass spectra were recorded on Bruker micrOTOF spectrometer. MS/MS spectra were acquired on Orbitrap Fusion™ Tribrid™ Mass Spectrometer (Thermo Fisher Scientific) equipped with electrospray ionization (ESI)
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), and the Thailand Research Fund (Grant No. RSA6080003). The authors are grateful to W. Pinyo from NSTDA Characterization and Testing Service Center (NCTC) for X-ray analysis.
References (29)
- et al.
Phytochemistry
(2008) - et al.
Nat. Prod. Res.
(2016) - et al.
Mycol. Res.
(1990) - et al.
Phytochemistry
(2002) - et al.
Tetrahedron
(1980) - et al.
Tetrahedron
(2006) - et al.
J. Nat. Prod.
(2019)et al.J. Nat. Prod.
(2015)et al.J. Antibiot.
(2017) - et al.
Syst. Biodivers.
(2009) - et al.
Eur. J. Biochem.
(2000) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—7th Ed. CLSI Document M7-A7
(2006)Performance Standards for Antimicrobial Susceptibility Testing; 16th Informational Supplement. CLSI Document M100-S16
(2006)
J. Appl. Microbiol.
Mycology
J. Org. Chem.
Mar. Drugs
Cited by (8)
Marine natural products
2022, Natural Product ReportsEndofungal bacteria boost anthelminthic host protection with the biosurfactant symbiosin
2022, Chemical Science