Aselacin C

Cyclopeptides usually play a pivotal role, either in the viability or virulence of fungi. Two types of cyclopeptides, six new hydroxamate siderophore cyclohexapeptides (1-6), including acremonpeptides E and F, and their complexes with aluminum and ferric ions; one new cyclic pentapeptolide, aselacin D (9); together with a known compound, aselacin C (10), were isolated and characterized from the sponge-derived fungus Acremonium persicinum F10. In addition, two new siderophore analogues chelating gallium ions (Ga3+), Ga (III)-acremonpeptide E (7) and Ga (III)-acremonpeptide F (8), using isolated acremonpeptides E and F, were prepared. The planar structures of 1-10 were elucidated by HRESIMS and (1D and 2D) NMR. The absolute configurations of amino acids were determined by means of the advanced Marfey's method and X-ray single-crystal diffraction analysis. X-ray fluorescence (XRF) spectrometer was performed to disclose the elements of compound 1, indicating the existence of aluminum (Al). Al (III)-acremonpeptides E (1), Ga (III)-acremonpeptides E (5), Al (III)-acremonpeptide F (7), and Ga (III)-acremonpeptide F (8) displayed high in vitro anti-fungal activities, which are comparable to amphotericin B, against Aspergillus fumigatus and Aspergillus niger. Keywords: Acremonium persicinum; acremonpeptides; anti-fungal activity; cyclopeptides; marine sponge-derived fungus; siderophore.

Three novel compounds, named the aselacins, which inhibit the binding of endothelin to its receptor have been isolated from two related Acremonium species of fungi grown in stationary culture. These compounds are cyclic pentapeptolides with a ring formed by cyclo[Gly-D-Ser-D-Trp-beta-Ala-L-Thr] and an additional exocyclic D-Gln to which is attached a functionalized long chain fatty acid. The aselacins differ in the functionalization of this acid. The structures of the aselacins were determined by amino acid analysis, mass spectrometry and evaluation of 1-D and 2-D homonuclear and heteronuclear 1H, 13C and 15N NMR spectra in protic and aprotic solvents. The stereochemistry of the amino acids present was elucidated by chiral HPLC of hydrolyzed compound.

A radioligand test to detect inhibitors of endothelin-1 binding to its receptors in bovine atrial and porcine cerebral membranes was used to screen fungal metabolites from stationary fermentations. Inhibitory activity, observed in culture extracts of two Acremonium species, led to the discovery of aselacins A, B and C. Aselacin A inhibits binding to both membrane fractions with IC50s of approximately 20 micrograms/ml.