Pyrenosetins A–C, New Decalinoylspirotetramic Acid Derivatives Isolated by Bioactivity-Based Molecular Networking from the Seaweed-Derived Fungus Pyrenochaetopsis sp. FVE-001

Abstract

Marine algae represent a prolific source of filamentous fungi for bioprospecting. In continuation of our search for new anticancer leads from fungi derived from the brown alga Fucus vesiculosus, an endophytic Pyrenochaetopsis sp. FVE-001 was selected for an in-depth chemical analysis. The crude fungal extract inhibited several cancer cell lines in vitro, and the highest anticancer activity was tracked to its CHCl3–soluble portion. A bioactivity-based molecular networking approach was applied to C18-SPE fractions of the CHCl3 subextract to predict the bioactivity scores of metabolites in the fractions and to aid targeted purification of anticancer metabolites. This approach led to a rapid isolation of three new decalinoylspirotetramic acid derivatives, pyrenosetins A–C (1–3) and the known decalin tetramic acid phomasetin (4). The structures of the compounds were elucidated by extensive NMR, HR-ESIMS, FT-IR spectroscopy, [α]D and Mosher’s ester method. Compounds 1 and 2 showed high anticancer activity against malignant melanoma cell line A-375 (IC50 values 2.8 and 6.3 μM, respectively), in line with the bioactivity predictions. This is the first study focusing on secondary metabolites of a marine-derived Pyrenochaetopsis sp. and the second investigation performed on the member of the genus Pyrenochaetopsis.

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

“…This indicated 1 to be a pentacyclic compound. Comparison of the NMR data of 1 with those of tetracyclic decalinoylspirotetramic acid derivatives pyrenosetins A-C [23] indicated close similarities. Thus, 1 was identified as a pyrenosetin-type decalinoylspirotetramic acid with an additional ring system.…”

“…Based on the phylogenetic tree analysis ( Figure S1), the strain FVE-087 was confirmed to be a Pyrenochaetopsis sp. The fungus FVE-087 was cultivated in the same manner as described in our previous study [23], i.e., in liquid potato dextrose medium (PDM) at 22 • C for 14 days under continuous shaking.…”

“…In-depth chemical investigation of the endophytic fungus Pyrenochaetopsis sp. FVE-001 by using a bioactivity-based molecular networking approach led to the rapid isolation and characterization of three new decalinoylspirotetramic acid derivatives pyrenosetins A-C and the known decalin phomasetin [23]. All four compounds showed notable activity against human malignant melanoma cancer cells (A-375) [23].…”

“…FVE-001 by using a bioactivity-based molecular networking approach led to the rapid isolation and characterization of three new decalinoylspirotetramic acid derivatives pyrenosetins A-C and the known decalin phomasetin [23]. All four compounds showed notable activity against human malignant melanoma cancer cells (A-375) [23]. In the continuation of our search for new anticancer metabolites from Fucus vesiculosis-associated fungi, a second strain of Pyrenochaetopsis sp.…”

Hetiamacin E and F, New Amicoumacin Antibiotics from Bacillus subtilis PJS Using MS/MS-Based Molecular Networking

“…In the last few decades, molecular networking has appeared as a rapidly emerging and developing a method for NPs discovery, helping researchers to decipher the metabolomic “dark matter” of the molecular world. A growing number of reports have described the application of molecular networking for effective chemical dereplication and novel NPs discovery [ 7 , 8 , 9 ]. For example, one successful application was the isolation of new monoterpene indole alkaloids obtained from the bark of Geissospermum leave , guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids [ 10 ].…”