Anti-Respiratory Syncytial Virus Prenylated Dihydroquinolone Derivatives from the Gorgonian-Derived Fungus <i>Aspergillus</i> sp. XS-20090B15

Abstract

Two new prenylated dihydroquinolone derivatives, 22-<i>O</i>-(<i>N</i>-Me-l-valyl)­aflaquinolone B (<b>1</b>) and 22-<i>O</i>-(<i>N</i>-Me-l-valyl)-21-<i>epi</i>-aflaquinolone B (<b>2</b>), and two known analogues, aflaquinolones A (<b>3</b>) and D (or a diastereomer of D, <b>4</b>), were isolated from the mycelia of a gorgonian-derived <i>Aspergillus</i> sp. fungus. The structures of the new compounds were elucidated by spectroscopic methods, ECD spectra, Marfey’s method, and chemical conversion. Compounds <b>1</b> and <b>2</b> display an unusual esterification of <i>N</i>-Me-l-Val to the side-chain prenyl group. Compound <b>2</b> exhibited outstanding anti-RSV activity with an IC₅₀ value of 42 nM, approximately 500-fold stronger than that of the positive control ribavirin (IC₅₀ = 20 μM), and showed a comparatively higher therapeutic ratio (TC₅₀/IC₅₀ = 520)