Discovery of Quassinoids and Indole Alkaloids With Antifouling Activity Against Barnacle Settlement From the Seeds of <i>Brucea javanica</i>

From the ethanol extract of Brucea javanica seeds, an undescribed C₁₉-type quassinoid, javanicolide I (1) and its epimer, javanicolide J (2), a new indole alkaloid, bruceolline O (3), a new-to-nature 1H-Indole-3-butanoic acid, α-methyl-γ-oxobutanoic acid (4), together with 13 known compounds (5-17) were isolated and structurally characterized by spectroscopic analysis. All compounds were evaluated for antifouling activity against Balanus amphitrite cyprid larval settlement. Aglycone of yadanzioside D (6) not only exhibits potent anti-settlement activity but also demonstrates low toxicity, with an EC₅₀ of 1.06 µg/mL and an LC₅₀/EC₅₀ ratio of 20.68 (>15, indicating low toxicity), outperforming the positive control SeaNine 211. Further resuscitation and zebrafish embryo assays also confirmed its low toxicity, highlighting its potential as a promising antifouling candidate.