Nitrogen-Containing Secondary Metabolites from a Deep-Sea Fungus Aspergillus unguis and Their Anti-Inflammatory Activity

Abstract

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were of isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.

Secondary Metabolites Diversity of Aspergillus unguis and Their Bioactivities: A Potential Target to Be Explored

“…The skeleton is basically two aromatic rings separated by two carbonyl groups. Although these compounds have already been isolated from other species of the genus Aspergillus , it was only in 2021 that the anthraquinones averantin ( 75 ), 7-chloroaverantin ( 76 ) and 1’-O-methylaverantion ( 77 ) were isolated from strains 158SC-067 of A. unguis [ 68 ].…”

“…Variations in the concentration or depletion of salts in the culture media proved to be an extremely interesting approach to produce new structures. The OSMAC strategy, despite having been successfully applied by several authors in A. unguis , can still be widely explored, changing the parameters of microorganism cultures, in order to allow the fungus to produce new chemical structures [ 28 , 30 , 68 ]. Approaches using epigenetic regulation also have not been widely used in A. unguis .…”

New Polyketide and Sesquiterpenoid Derivatives from the Magellan Seamount‐Derived Fungus Penicillium rubens AS‐130

“…[1] Given the fact that deep sea-derived fungi have been regarded as an invaluable source of bioactive secondary metabolites with diverse chemical structures, [2,3] the fungi surviving in the deep sea seamount areas are attracting more and more attentions due to their great potential in secondary metabolism. Up to now, a diverse array of secondary metabolites with potential biological and pharmacological activities have been isolated from the deep-sea derived fungi, including indole diketopiperazine, [4] tanzawaic acids, [5] cytochalasin, [6] macrolide, [7] and diterpenes, [8] which exhibited antibacterial, [9] cytotoxic, [10] anti-proliferative, [11] anti-HIV, [12] and antiinflammatory [13] activities.…”

Aspersterols A–D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus Aspergillus unguis

“…The genus Aspergillus is known as a major contributor of fungal steroids, and recently, several series of novel steroids with rearranged structures and promising activities have been reported from this genus. , In our continuous studies to discover bioactive molecules from marine-derived fungi, Aspergillus unguis IV17-109 was recently found to be a producer of nidulin-related polyketides and nitrogenous metabolites, which showed antimicrobial and anti-inflammatory activities. , Guided by NMR, it was found that the100% MeOH fraction of the EtOAc extract from A. unguis IV17-109 showed some interesting peaks in the aliphatic region, which differed from nidulin-related compounds. Purification of metabolites in this fraction led to the isolation of a rare group of ergostane-type sterols with conjugated double bonds at Δ 17 and Δ 22 , aspersterols A–D ( 1 – 4 ), and a known congener ( 5 ).…”