The emerging outbreak of bacterial
diseases is a major
challenge
for the aquaculture industry. The development of new antibacterial
agents from natural resources to curb fish bacterial diseases in aquaculture
is becoming increasingly popular. In this study, eight new benzoic
acid-containing alkaloids, asperalin A–F (1–6), asperalumazine A (7), and N-(3-acetamidopropyl)-3,4-dihydroxybenzamide (8), along
with four known compounds (9–12)
were isolated and identified from a seagrass-derived Aspergillus
alabamensis. Their chemical structures were established on
the basis of extensive spectroscopic analyses (including HRESIMS,
1D and 2D NMR spectroscopy), NMR computational methods, and electronic
circular dichroism (ECD) calculations. Compounds 1–6 exhibited moderate or potent inhibitory activities against
at least one fish pathogenic bacterium, among Edwardsiella
ictalurid, Streptococcus iniae, and Streptococcus parauberis, and these compounds represent
the first report of the coupling of dihydroquinolone alkaloids with
benzoic acid derivatives. Compounds 3 and 4 showed strong activities against Staphylococcus aureus, S. iniae, and S. parauberis,
with an MIC value of 10.1, 5.0, and 10.1 μM, respectively. Compound 5, an N-alkylated product of 4, exhibited the strongest inhibitory effects against S. iniae, with an MIC value of 2.2 μM. Notably, compound 6, as a new natural bactericide, showed moderate to potent inhibitory
activity toward all strains tested, including one Gram-negative bacterium E. ictalurid (10.9 μM, MIC) and four Gram-positive
bacteria S. iniae (43.6 μM, MIC), S.
aureus (21.8 μM, MIC), S. parauberis (87.3 μM, MIC), and Bacillus subtilis (21.8
μM, MIC). Compound 7 represents the first example
of a lumazine derivative directly coupled to a benzoic acid moiety
by a hydroxymethyl group.