Discovery new marine-derived terphenyllin derivatives as potential antifoulants through structural optimization

Abstract

Marine biofouling remains a global problem, harming the maritime industries and ocean's ecosystem. Toxic antifoulants caused serious environmental pollution, which may enter human body through the food chain and affect human health. We searched for antifouling active compounds from the marine compound library, and a natural p-terphenyl metabolite, terphenyllin (1) and its derivatives (2–8) attracted our attention. Two 2′ or 4″ hydroxy group etherified derivatives (4 and 5) of terphenyllin showed antialgal activity. To improve its activity, twenty-four new terphenyllin derivatives (9–21, 23–27, and 29–34), along with two know derivatives (22 and 28), were designed and semisynthesized by halogenation, etherification, and acylation reactions. All the compounds were evaluated for their antifouling activity against diatoms Navicula Exigua, N. Leavissima, Amphora Ovalis, Skeletonema Costatum, and Nitzschia closterium f. minutissima. Twelve compounds (9–11, 19, 22–25, 28, 30–31, and 34) displayed antialgal activities with EC₅₀ values from 1.2 to 9.8 μg/mL. Especially, compounds 10, 11, and 25 exhibited promising broad-spectrum antifouling activity (EC₅₀ = 1.2–3.6 μg/mL) with lower ecotoxicity (LC₅₀ > 150 μg/mL), which were approximately equivalent to the commercial antifouling agent Econea (EC₅₀ = 0.5–1.1 μg/mL). It was worth noting that compound 9 (EC₅₀ = 2.0 μg/mL, LC₅₀ > 150 μg/mL) showed potential antifouling activity against the settlement of the macrofouling species Mussel Mytilus edulis. The preliminary structure−activity relationships of these compounds were also discussed. In conclusion, this study provided promising antifouling compounds, which were poised for further development as new environmentally friendly antifoulants.