Pyrenosetin D, a New Pentacyclic Decalinoyltetramic Acid Derivative from the Algicolous Fungus Pyrenochaetopsis sp. FVE-087

Abstract

The fungal genus Pyrenochaetopsis is commonly found in soil, terrestrial, and marine environments, however, has received little attention as a source of bioactive secondary metabolites so far. In a recent work, we reported the isolation and characterization of three new anticancer decalinoyltetramic acid derivatives, pyrenosetins A–C, from the Baltic Fucus vesiculosus-derived endophytic fungus Pyrenochaetopsis sp. FVE-001. Herein we report a new pentacyclic decalinoylspirotetramic acid derivative, pyrenosetin D (1), along with two known decalin derivatives wakodecalines A (2) and B (3) from another endophytic strain Pyrenochaetopsis FVE-087 isolated from the same seaweed and showed anticancer activity in initial screenings. The chemical structures of the purified compounds were elucidated by comprehensive analysis of HR-ESIMS, FT-IR, [α]D, 1D and 2D NMR data coupled with DFT calculations of NMR parameters and optical rotation. Compounds 1–3 were evaluated for their anticancer and toxic potentials against the human malignant melanoma cell line (A-375) and the non-cancerous keratinocyte cell line (HaCaT). Pyrenosetin D (1) showed toxicity towards both A-375 and HaCaT cells with IC50 values of 77.5 and 39.3 μM, respectively, while 2 and 3 were inactive. This is the third chemical study performed on the fungal genus Pyrenochaetopsis and the first report of a pentacyclic decalin ring system from the fungal genus Pyrenochaetopsis.

Density Functional Theory (DFT)-Aided Structure Elucidation of Linear Diterpenes from the Irish Brown Seaweed Bifurcaria bifurcata

“…Absolute configuration of compound 1 was determined using DFT prediction of optical rotation (OR) [ 17 , 18 , 19 ], using the same set of optimized conformers of model compound 1s ( Figure 2 ) that were used for NMR chemical shift prediction. In doing so, we made the reasonable assumption that the contribution to chiroptical properties, including molar rotation, of a remote non-chiral side chain is negligible [ 11 ].…”

The Essentials of Marine Biotechnology

“…To determine the absolute configuration of metabolites, singlecrystal X-ray diffraction, NMR advanced Mosher's methods (for alcohols), Marfey's method (for aminoacids) are often used (Bhushan and Brückner, 2011;Cimmino et al, 2017). Computational approaches such as density functional theory (DFT) coupled with (i) NMR, (ii) chiroptical methods e.g., electronical circular dichroism (ECD), vibrational circular dichroism (VCD) spectroscopy and (iii) optical rotation are being successfully employed in identification of relative and absolute configuration of marine natural products (Merten et al, 2015;Batista et al, 2018;Menna et al, 2019;Wang and Hamann, 2019;Fan et al, 2020;Marcarino et al, 2020;Zhu and Sun, 2020). The elucidation of biosynthetic pathways from genomic sequence data is also used to support the absolute configuration assignment (Hu et al, 2018;Kim et al, 2020).…”

Potential of Anti-Cancer Activity of Secondary Metabolic Products from Marine Fungi

“…The results revealed high activity against lymphoma cancer cells (U937) with IC 50 value at 500 µg/mL of β-cyclodextrin-Asparaginase nanobiocomposite. Golbabaie et al [11] used a crude L-Asparaginase enzyme mixed with cell viability to investigate the anti-cancer activity against K562 and HL60 cancer cell lines and lymphoblastic leukemia. The results revealed that the toxicity of the enzyme was determined with IC 50 values were calculated as 0.4 and 0.5 IU/mL for K562 and HL60 respectively.…”

“…The toxicity of L-asparaginase against K562 and HL60 cancer cell lines and L6 as normal cells was determined with IC 50 values were calculated as 0.4 and 0.5 IU/mL for K562 and HL60 respectively [11] Childhood leukemia L-Asparaginase with a dose of ≥ 6000 IU/sq m three times weekly.…”

“…The asparaginase enzyme which has been isolated from A. niger [4], A. tubingensis [5] A. terreus [6], Fusarium sp. [7], Talaromyces pinophilus [8], Trichosporon asahii [9], Trichoderma viride [10], and Sarocladium strictum [11] was recorded as the most anticancer properties among other several enzymes. Besides, several new anticancer products have been isolated and identified from the secondary metabolic production of marine fungi such as Gliotoxin which was isolated from Aspergillus sp.…”