Overcoming environmental problems of biocides: Synthetic bile acid derivatives as a sustainable alternative

Marine biofouling represents a global economic and ecological challenge. Some marine organisms produce bioactive metabolites, such as steroids, that inhibit the settlement and growth of fouling organisms. The aim of this work was to explore bile acids as a new scaffold with antifouling (AF) activity by using chemical synthesis to produce a series of bile acid derivatives with optimized AF performance and understand their structure-activity relationships. Seven bile acid derivatives were successfully synthesized in moderate to high yields, and their structures were elucidated through spectroscopic methods. Their AF activities were tested against both macro- and microfouling communities. The most potent bile acid against the settlement of Mytilus galloprovincialis larvae was the methyl ester derivative of cholic acid (10), which showed an EC50 of 3.7 mu M and an LC50/EC50 > 50 (LC50 > 200 mu M) in AF effectiveness vs toxicity studies. Two derivatives of deoxycholic acid (5 and 7) potently inhibited the growth of biofilm-forming marine bacteria with EC50 values < 10 mu M, and five bile acids (1, 5, and 7-9) potently inhibited the growth of diatoms, showing EC50, values between 3 and 10 mu M. Promising AF profiles were achieved with some of the synthesized bile acids by combining antimacrofouling and antimicrofouling activities. Initial studies on the incorporation of one of these promising bile acid derivatives in polymeric coatings, such as a marine paint, demonstrated the ability of these compounds to generate coatings with antimacrofouling activity.