Design, synthesis and biological evaluation of soluble 2,5-diketopiperazines derivatives as potential antifouling agents

Abstract

A small library of soluble 2,5-diketopiperazine derivatives were designed, synthesized and evaluated as antifouling agents against two species of marine organisms: Balanus amphitrite and Bugula neritina by larval attachment assay. The results showed that different derivatives had different antifouling activities. Among these compounds, 3a (EC₅₀ = 2.5 μg mL⁻¹), 3b (EC₅₀ = 3.2 μg mL⁻¹) and 3d (EC₅₀ = 1.6 μg mL⁻¹) had strong activities, and 2d (EC₅₀ = 20.5 μg mL⁻¹), 3l (EC₅₀ = 25.0 μg mL⁻¹) and 3m (EC₅₀ = 18.5 μg mL⁻¹) had moderate activities against Balanus amphitrite, but other compounds had no activities. Differently, compounds 3d (EC₅₀ = 3.1 μg mL⁻¹) and 3i (EC₅₀ = 2.3 μg mL⁻¹) exhibited strong activities, and 3a (EC₅₀ = 11.3 μg mL⁻¹) and 3c (EC₅₀ = 17.2 μg mL⁻¹) showed moderate activities against Bugula neritina, whereas other compounds had no activities. All of the active compounds had stronger antifouling activities than those of the natural product cyclo-(L-Phe-L-Pro). Compound 3d could be a new template molecule for further development as an antifouling agent because of its strong inhibitory activities against both species of fouling organisms with low or no toxicity to the environment.