New Natural Products from the Sponge-Derived FungusAspergillus niger

Abstract

Fractionation of the EtOAc extract of a static culture of Aspergillus niger isolated from the Mediterranean sponge Axinella damicornis yielded eight secondary metabolites, out of which seven compounds (2-8) proved to be new natural products, whereas one was identified as the known fungal pigment cycloleucomelone (1). The new compounds included the 3,3'-bicoumarin bicoumanigrin (2), the structurally unusual 4-benzyl-1H-pyridin-6-one derivatives aspernigrins A and B (3 and 4), and pyranonigrins A-D (5-8), the latter featuring a novel pyrano[3,2-b]pyrrole skeleton hitherto unprecedented in nature. All structures were elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies ((1)H, (13)C, COSY, HMQC, HMBC, NOE difference spectra) and mass spectral analysis. For the two chiral molecules 4 and 5, the absolute configurations were established by quantum chemical calculations of their circular dichroism (CD) spectra. In each case, two independent methods, i.e., a molecular dynamics approach taking into consideration the molecular flexibility, and a conformational analysis followed by Boltzmann weighting of the single CD spectra calculated for the conformers thus obtained, led to identical results without the need of any empirical comparison of chiroptical data reported for reference compounds. Bicoumanigrin (2) showed moderate cytotoxicity against human cancer cell lines in vitro. In addition, aspernigrin B (4) was found to display a strong neuroprotective effect against glutamic acid.

Aspernigrins with anti-HIV-1 activities from the marine-derived fungus Aspergillus niger SCSIO Jcsw6F30

“…14 by its 1 H, 13 C NMR and OR data (((½a 20 D À24.2, c 0.1, CHCl 3 ). Compounds 6-8 were identified as rubrofusarin (6), rubrofusarin B (7), and fonsecin (8) 15 by comparison with their 1 H and 13 C NMR with those reported.…”

“…5 Compounds 1 and 2 were identified as aspernigrins A and B by comparison of their NMR, MS and optical rotation (OR) data with those available in the literature. 6,7 The structures of aspernigrins A and B were identified as 2-pyridone substructure initially, 6 and then revised to be 4-pyridone. 7,8 The OR data of 2 (½a 20 D +38.5, c 0.1, DMSO) suggests it has the same S-configuration (C-7 0 ) with aspernigrin B in the reference (½a 20 D +37.8, c 0.5, DMSO).…”

“…Discovery of anti-HIV-1agents, especially with novel modes of action, from marine organisms is becoming more attractive and promising. 2 During our continuous chemical study of marine-derived fungi, four 2-benzylpyridin-4-one-containing metabolites (1-4), including two structurally new aspernigrins C (3) and D (4), and other four known compounds (5)(6)(7)(8) were isolated from the marinederived black aspergilli, Aspergillus niger SCSIO Jcsw6F30 (Fig. 1).…”

“…7,8 The OR data of 2 (½a 20 D +38.5, c 0.1, DMSO) suggests it has the same S-configuration (C-7 0 ) with aspernigrin B in the reference (½a 20 D +37.8, c 0.5, DMSO). 6 Aspernigrin C (3) 9 was suggested to be an N-acylcarboxyamide derivate, like the structures of pestalamide B 10 and nygerone A, 11 connected by 2-methylsuccinic acid moiety to the carboxamide of aspernigrin B (2), by HR-ESI-MS and NMR analysis. The planer structure of aspernigrin C (3), together with some key HMBC correlations, was showed in Figure 2 as a new compound.…”

“…6 However, antiviral activities of aspernigrins had never been found before. Now, in our study, the structurally new compound aspernigrin C (3) and aspernigrin A (1) showed potent and weak efficacy in inhibiting HIV-1 infection, respectively, while aspernigrins B (2) and D (4) showed no antiviral activities.…”