Azaphilones: a class of fungal metabolites with diverse biological activities

Abstract

This review presents an overview of azaphilones isolated from different species of fungi, detailing their chemical structures and biological activities as covered in the recent literature. Over 170 different azaphilone compounds occur in fungi belonging to 23 genera from 13 families: these azaphilones can be classified into ten different structural groups. Numerous azaphilone structures have been described, particularly from members of the Trichocomaceae and Xylariaceae families. Azaphilones exhibit a wide range of interesting biological activities, such as antimicrobial, antifungal, antiviral, antioxidant, cytotoxic, nematicidal and anti-inflammatory activities. Many of these effects may be explained by the reactions of azaphilones with amino groups, such as those found in amino acids, proteins and nucleic acids, resulting in the formation of vinylogous c-pyridones.

Penidioxolanes A and B, 1,3-Dioxolane Containing Azaphilone Derivatives from Marine-derivedPenicilliumsp. KCB12C078

“…4 Among these various bioactive compounds, azaphilone family has been isolated from fungi belonging to 23 genera from 13 families, such as, Aspergillus, Penicillium, Chaetomium, Talaromyces, Pestalotiopsis, Phomopsis, Emericella, and Epicoccum, as well as Monascus and Hypoxylon sp.. Several azaphilones are unique to one species and constitute taxonomically important marker metabolites. 5,6 Azaphilone family are structurally diverse pigments, mostly secondary metabolites of fungal origin, and are highly oxygenated bicyclic rings showing various biological activities, including antimicrobial, antifungal, antiviral, antioxidant, cytotoxic, nematicidal and anti-inflammatory activities.…”

Isochromophilones from an endophytic fungus Diaporthe sp.

“…The name of azaphilone arose as a result of their affinity for ammonia: the pigments react with amines, such as proteins, amino acids and nucleic acids, to form red and purple vinylogous -pyridones due to the exchange of pyrane oxygen for nitrogen [1][2][3] . Azaphilone compounds had a wide range of bioactivities including cytotoxic, antifungal, antimicrobial, antioxidant and antiinflammatory activities, [4][5][6][7][8] and could be generally produced by Penicillium, Chaetomium and Monascus.…”

“…Azaphilone compounds had a wide range of bioactivities including cytotoxic, antifungal, antimicrobial, antioxidant and antiinflammatory activities, [4][5][6][7][8] and could be generally produced by Penicillium, Chaetomium and Monascus. 3 In the course of our search for novel and/or bioactive metabolites from microbes lived in special niche, 4,9,10 five azaphilones including three new isochromophilones X-XII (1-3) and two known compounds sclerotioramine (4) 11 and isochromophilone VI (5) 12 were isolated from the solid-substrate fermentation cultures of an endophytic fungus Diaporthe sp. The structures were identified on the basis of extensive spectroscopic methods.…”

“…The structures were identified on the basis of extensive spectroscopic methods. The cytotoxic activities of compounds (1)(2)(3)(4)(5) (5) could be replaced by a benzene ring in compound 1. To confirm the proposed structure, extensive NMR spectra have been investigated (Figure 2).…”

“…13,14 Furthermore, the 14S-configurations of 1-3 were determined by comparing their NMR data of the side chain moieties with those of similar azaphilone compounds, isochromophilone Ia, IIa and rotiorinol A. 15,16 Biosynthetically, azaphilone was derived from the polyketide pathway, 3,17 whose oxygen atom could be further substituted by primary amines or ammonia into N-containing compounds rapidly. 1 For example, sclerotiorin could be converted to sclerotioramine (4) with ammonia.…”