Bioactive Hydroanthraquinones and Anthraquinone Dimers from a Soft Coral-Derived Alternaria sp. Fungus

Abstract

Five new hydroanthraquinone derivatives, tetrahydroaltersolanols C-F (1-4) and dihydroaltersolanol A (5), and five new alterporriol-type anthranoid dimers, alterporriols N-R (12-16), along with seven known analogues (6-11 and 17), were isolated from the culture broth and the mycelia of Alternaria sp. ZJ-2008003, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra as well as single-crystal X-ray crystallography. Compound 13 represents the first isolated alterporriol dimer with a C-4-C-4' linkage, and the absolute configuration of 4 was determined using the modified Mosher's method. Compounds 1 and 15 exhibited antiviral activity against the porcine reproductive and respiratory syndrome virus (PRRSV), with IC₅₀ values of 65 and 39 μM, respectively. Compound 14 showed cytotoxic activity against PC-3 and HCT-116 cell lines, with IC₅₀ values of 6.4 and 8.6 μM, respectively.

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

“…This enzyme, which shares similarities with dihydroflavonol-4-reductases of plants (27), catalyzes the dimerization of hydroxylated dihydrokalafungin to produce the benzoisochromanequinone actinorhodin (26). A number of dimeric anthrones have been isolated from fungi (7,14,28), with strong evidence that their formation is also enzymatically catalyzed (14). However, no fungal enzyme involved in catalyzing their formation has yet been reported.…”

“…Nataloe-emodin 10 dimers with alternative aryl-aryl bonds have not been observed in C. fulvum, and they do not have dimeric forms of emodin 5, which suggests that ClaM might be highly selective for both substrate and type of linkage that it catalyzes. In contrast, Alternaria species produce a large variety of alterporriol compounds, which are heterodimers of macrosporin and altersolanol exhibiting various couplings, including C5-C5′, C1-C7′, C7-C5′, and C2-C2′ bonds (28,33). Homodimers of macrosporin or altersolanol were also isolated and show C4-C6′ and C4-C8′ bonds (28).…”

“…In contrast, Alternaria species produce a large variety of alterporriol compounds, which are heterodimers of macrosporin and altersolanol exhibiting various couplings, including C5-C5′, C1-C7′, C7-C5′, and C2-C2′ bonds (28,33). Homodimers of macrosporin or altersolanol were also isolated and show C4-C6′ and C4-C8′ bonds (28). The diversity of dimers for a given anthraquinone likely depends on both substrates and specificity of enzymes involved in dimerization.…”

AlternariaMycotoxins in Food and Feed: An Overview

“…So far, several compounds of the alterporriol and altersolanol families have been reported, including the emerging Alternaria toxins macrosporin A and altersolanol A (As-A) [40], which exhibited antibacterial activity [41].…”

The Anthraquinone Derivatives from the Fungus Alternaria sp. XZSBG-1 from the Saline Lake in Bange, Tibet, China

“…Anthraquinones and tetrahydroanthraquinones are widely distributed as secondary metabolites in natural biosources, and show important biological activities [2][3][4][5]. So far, 18 compounds of alterporriol family [6][7][8][9][10][11][12] and 14 compounds of altersolanol family [9,[13][14][15][16] have been reported. Herein, we report that the isolation, elucidation and biological activities of the anthraquinone and tetrahydroanthraquinone derivatives from Alternaria sp.…”