Synthesis and Antifouling Activity Evaluation of Analogs of Bromosphaerol, a Brominated Diterpene Isolated from the Red Alga <i>Sphaerococcus coronopifolius</i>
Kyriakos C. Prousis,
Stefanos Kikionis,
Efstathia Ioannou,
Silvia Morgana,
Marco Faimali,
Veronica Piazza,
Theodora Calogeropoulou,
Vassilios Roussis
Affiliations
Kyriakos C. Prousis
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11653 Athens, Greece
Stefanos Kikionis
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Efstathia Ioannou
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Silvia Morgana
Institute for the Study of Anthropic Impacts and Sustainability in Marine Environment (IAS), National Research Council (CNR), Via De Marini 6, 16149 Genova, Italy
Marco Faimali
Institute for the Study of Anthropic Impacts and Sustainability in Marine Environment (IAS), National Research Council (CNR), Via De Marini 6, 16149 Genova, Italy
Veronica Piazza
Institute for the Study of Anthropic Impacts and Sustainability in Marine Environment (IAS), National Research Council (CNR), Via De Marini 6, 16149 Genova, Italy
Theodora Calogeropoulou
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11653 Athens, Greece
Vassilios Roussis
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Marine biofouling is an epibiotic biological process that affects almost any kind of submerged surface, causing globally significant economic problems mainly for the shipping industry and aquaculture companies, and its prevention so far has been associated with adverse environmental effects for non-target organisms. Previously, we have identified bromosphaerol (1), a brominated diterpene isolated from the red alga Sphaerococcus coronopifolius, as a promising agent with significant antifouling activity, exerting strong anti-settlement activity against larvae of Amphibalanus (Balanus) amphitrite and very low toxicity. The significant antifouling activity and low toxicity of bromosphaerol (1) motivated us to explore its chemistry, aiming to optimize its antifouling potential through the preparation of a number of analogs. Following different synthetic routes, we successfully synthesized 15 structural analogs (2–16) of bromosphaerol (1), decorated with different functional groups. The anti-settlement activity (EC50) and the degree of toxicity (LC50) of the bromosphaerol derivatives were evaluated using cyprids and nauplii of the cirriped crustacean A. amphitrite as a model organism. Derivatives 2, 4, and 6–16 showed diverse levels of antifouling activity. Among them, compounds 9 and 13 can be considered as well-performing antifoulants, exerting their activity through a non-toxic mechanism.