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

ABSTRACT From the ethanol extract of Brucea javanica seeds, an undescribed C 19 ‐type quassinoid, javanicolide I ( 1 ) and its epimer, javanicolide J ( 2 ), a new indole alkaloid, bruceolline O ( 3 ), a new‐to‐nature 1 H ‐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 EC 50 of 1.06 µg/mL and an LC 50 /EC 50 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.