Azaphilones from the Red Sea Fungus <i>Aspergillus falconensis</i>

• Main Authors: Dina H. El-Kashef, Fadia S. Youssef, Rudolf Hartmann, Tim-Oliver Knedel, Christoph Janiak, Wenhan Lin, Irene Reimche, Nicole Teusch, Zhen Liu, Peter Proksch
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Marine Drugs
• Subjects: <i>Aspergillus falconensis</i>; OSMAC; azaphilones; X-ray diffraction; NF-κB inhibition
• Online Access: https://www.mdpi.com/1660-3397/18/4/204

The marine-derived fungus <i>Aspergillus falconensis</i>, isolated from sediment collected from the Canyon at Dahab, Red Sea, yielded two new chlorinated azaphilones, falconensins O and P (<b>1</b> and <b>2</b>) in addition to four known azaphilone derivatives (<b>3</b>−<b>6</b>) 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 (<b>7</b>−<b>9</b>) including two brominated derivatives (<b>7</b> and <b>8</b>) together with three known analogues (<b>10</b>−<b>12</b>). 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 <b>5</b>, comparison of NMR data and optical rotations as well as on biogenetic considerations. Compounds <b>1</b>, <b>3</b>−<b>9</b>, and <b>11</b> 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.