Azaphilones from the Red Sea Fungus Aspergillus falconensis

Abstract

The marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Canyon at Dahab, Red Sea, yielded two new chlorinated azaphilones, falconensins O and P (1 and 2) in addition to four known azaphilone derivatives (3-6) following fermentation of the fungus on solid rice medium containing 3.5% NaCl. Replacing NaCl with 3.5% NaBr induced accumulation of three additional new azaphilones, falconensins Q-S (7-9) including two brominated derivatives (7 and 8) together with three known analogues (10-12). The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and HRESIMS data as well as by comparison with the literature. The absolute configuration of the azaphilone derivatives was established based on single-crystal X-ray diffraction analysis of 5, comparison of NMR data and optical rotations as well as on biogenetic considerations. Compounds 1, 3-9, and 11 showed NF-κB inhibitory activity against the triple negative breast cancer cell line MDA-MB-231 with IC₅₀ values ranging from 11.9 to 72.0 µM.

Keywords: Aspergillus falconensis; NF-κB inhibition; OSMAC; X-ray diffraction; azaphilones.

Figure 1

Structures of azaphilones isolated from A. falconensis.

Figure 2

Molecular structure of 5 from a single-crystal X-ray structure determination (50% thermal ellipsoids; H atoms with arbitrary radii). The propyl group is disordered, and the two respective atom positions were refined with equal occupation factors.