Lead optimization in the search for new antifouling compounds

Innovative environmentally friendly technologies to combat marine biofouling is a practical and urgent need, since the associated economic, environmental, and human health consequences are enormous. Although the addition of biocides to marine paint coatings has been the most used solution to avoid marine biofouling, currently applied biocides are persistent, bioaccumulative, and toxic to the oceans.

The most promising alternatives for fouling protection focus on the development of coatings whose active ingredients are natural products or lab-synthesized products inspired by natural compounds. The recent identification of a lead compound by our lab group sparked the search for new compounds with optimized properties and therefore a small library of new nine synthetic compounds was obtained. The synthesis of these compounds was accomplished in two steps, with yields between 18-88%.

An optimization was successfully accomplished for a structure-related polyphenolic compound, concerning potency (EC₅₀ = 2.74 µM) against the settlement of the larvae of Mytilus galloprovincialis and lipophilicity, which will increase compatibility with paint formulations (LogKow = -0.79). Moreover, the new optimized compound showed no toxicity against the non-target organism Artemia salina, similar to GAP.

This optimized compound will proceed for further studies, namely the mechanism of action exploration.