Brevianamide K

Anti-Neuroinflammatory Effects of Prenylated Indole Alkaloids from the Antarctic Fungus Aspergillus sp. Strain SF-7367.[Pubmed:39860162]

Molecules. 2025 Jan 13;30(2):294.

Inflammation has always been considered a trigger or consequence of neurodegenerative diseases, and the inhibition of inflammation in the central nervous system can effectively protect nerve cells. Several studies have indicated that various natural products inhibit neuroinflammation. Among these, Antarctic fungal metabolites have pharmacological activities and a developmental value. Therefore, this study aimed to evaluate the anti-neuroinflammatory activity of an Antarctic fungus belonging to Aspergillus (strain SF-7367). Secondary metabolites of SF-7367 were isolated using high-performance liquid chromatography followed by validation of their anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglia and RAW264.7 macrophages. Chemical analysis of metabolites from the fungal strain revealed five known compounds: epideoxybrevianamide E (1), brevianamide V/W (2), Brevianamide K (3), brevianamide Q (4), and brevianamide R (5). Among these compounds, Brevianamide K showed significant anti-inflammatory activity against both cell types. Results of Western blotting and molecular docking showed that Brevianamide K could regulate the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappaB) signaling. This indicates that Brevianamide K present in Aspergillus sp. (strain SF-7367) can inhibit inflammatory responses by reducing lipopolysaccharide-induced nuclear translocation of NF-kappaB (p65). These findings suggest that Aspergillus sp. (strain SF-7367) and Brevianamide K are candidate agents for treating neurodegenerative diseases.

Hydroxylation with Unusual Stereoinversion Catalyzed by an Fe(II) /2-OG Dependent Oxidase and 3,6-Diene-2,5-diketopiperazine Formation in the Biosynthesis of Brevianamide K.[Pubmed:36750406]

Angew Chem Int Ed Engl. 2023 Mar 27;62(14):e202216989.

Natural products with the 3,6-diene-2,5-diketopiperazine core are widely distributed in nature; however, the biosynthetic mechanism of 3,6-diene-2,5-diketopiperazine in fungi remains to be further elucidated. Through heterologous expression and biochemical investigation of an Fe(II) /2-oxoglutarate-dependent oxidase (AspE) and a heme-dependent P450 enzyme (AspF), we report that AspE, AspF and subsequent dehydration account for the formation of the 3,6-diene-2,5-diketopiperazine substructure of Brevianamide K from Aspergillus sp. SK-28, a symbiotic fungus of mangrove plant Kandelia candel. More interestingly, in-depth investigation of the enzymatic mechanism showed that AspE promotes hydroxylation of brevianamide Q with unprecedented stereoinversion through hydrogen atom abstraction and water nucleophilic attack from the opposite face of the resultant iminium cation intermediate.

Diketopiperazine and Diphenylether Derivatives from Marine Algae-Derived Aspergillus versicolor OUCMDZ-2738 by Epigenetic Activation.[Pubmed:30583513]

Mar Drugs. 2018 Dec 22;17(1):6.

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (‒)-brevianamide R ((‒)-3), (+)-brevianamide Q ((+)-4), (‒)-brevianamide Q ((‒)-4), brevianamide V ((+)-5), brevianamide W ((‒)-5), Brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (‒)-brevianamide X ((+)- and (‒)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 microM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1(-)4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (+/-)-3, (+/-)-4, and (+/-)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 muM, respectively. Compound 10 exhibited better alpha-glucosidase inhibitory activity than the assay control acarbose with IC(50) values of 117.3 and 255.3 muM, respectively.

Secondary metabolites from an algicolous Aspergillus versicolor strain.[Pubmed:22363226]

Mar Drugs. 2012 Jan;10(1):131-139.

Two new compounds, asperversin A (1) and 9xi-O-2(2,3-dimethylbut-3-enyl)brevianamide Q (2), and nine known compounds, Brevianamide K (3), brevianamide M (4), aversin (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O-methylaverufin (7), 6-O-methylaverufin (8), 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (9), ergosta-7,22-diene-3beta,5alpha,6beta-triol (10), and 6beta-methoxyergosta-7,22-diene-3beta,5alpha-diol (11), were obtained from the culture of Aspergillus versicolor, an endophytic fungus isolated from the marine brown alga Sargassum thunbergii. The structures of these compounds were established by spectroscopic techniques. Compounds 4, 7 and 8 exhibited antibacterial activities against Escherichia coli and Staphyloccocus aureus, and 7 also showed lethality against brine shrimp (Artemia salina) with an LC(5)(0) value of 0.5 mug/mL.

Brevianamide J, a new indole alkaloid dimer from fungus Aspergillus versicolor.[Pubmed:19627104]

Org Lett. 2009 Aug 20;11(16):3714-7.

Brevianamide J (1), a new indole alkaloid dimer, was isolated together with four new diketopiperazine alkaloids (Brevianamide K-N, 2-5) from the solid-state fermented culture of Aspergillus versicolor. Their structures were elucidated on the basis of spectral data. X-ray crystallographic analysis confirmed the structures of 1 and 4.

Brevianamide K (CAS 1174538-66-9) is a natural product offered by BioCrick for research applications. Customers can buy or order Brevianamide K from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.