Antialgal compounds from Codium fragile: Isolation, identification and inhibitory effects on red tide microalgae

Harmful algal blooms (HABs, or red tides) pose significant threats to marine ecosystems and aquaculture, creating an urgent need for eco-friendly algicides. This study aimed to identify natural antialgal agents from the macroalga Codium fragile using a bioactivity-guided isolation approach. Six compounds were isolated and identified: myristic acid (1), 7-hydroxyheptanoic acid (2), 15-nor-amorph-11-en-4β-ol (3), 3,7-dimethyloctane-1,7-diol (4), oleic acid (5), and loliolide (6). Among these, myristic acid, oleic acid, and loliolide exhibited selective growth inhibition against six red tide microalgae, with EC₅₀-96h values ranging from 14.2 to > 500 μg/mL. Notably, oleic acid showed superior potency against Heterosigma akashiwo (EC₅₀ = 12.4 μg/mL) and Phaeocystis globosa (EC₅₀ = 15.8 μg/mL) compared to potassium dichromate. Morphological observations revealed that these compounds induced distinct cellular alterations (shrinkage, swelling, rupture, and collapse), which differed from those caused by potassium dichromate, suggesting different inhibitory mechanisms. This study provides promising candidates for eco-friendly algicide development and establishes a methodological framework for isolating antialgal compounds from macroalgae.