Synthesis and Antifouling Activity Evaluation of Analogs of Bromosphaerol, a Brominated Diterpene Isolated from the Red Alga Sphaerococcus coronopifolius.

Kyriakos C Prousis,Silvia Morgana,Stefanos Kikionis,Efstathia Ioannou,Veronica Piazza,Theodora Calogeropoulou,Vassilios Roussis,Marco Faimali

doi:10.3390/md20010007

Abstract

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.

Highlights

Marine biofouling is an epibiotic biological process that is characterized by the attachment of various micro- and macro-organisms of the marine environment on submerged surfaces [1,2,3,4,5]
In the framework of our research investigations, we have previously identified bromosphaerol (1), a brominated diterpene isolated from the red alga Sphaerococcus coronopifolius, as a promising agent with significant antifouling activity [36,37]
Our strategy for obtaining initial structure-antifouling activity relationships for bromosphaerol involved (a) introducing polar groups at C-1 and/or C-2 (2–6 and 8), (b) removing the C-11 hydroxyl group (9 and 10), and (c) substituting C-2 with functional groups, while the ∆1 double bond was repositioned to C-1–C-10 to allow for the generation of an extended conjugated system (7 and 11–16)

Summary

Introduction

Marine biofouling is an epibiotic biological process that is characterized by the attachment of various micro- and macro-organisms of the marine environment on submerged surfaces [1,2,3,4,5]. Marine biofouling represents a global phenomenon generating undoubtedly profound economic and ecological problems that needs to be addressed vigorously. It affects almost any kind of submerged surface, including aquaculture systems, coastal electric power stations, various underwater constructions, and marine vessels [10,11,12]. The attachment of microbial slimes, algae, and marine sessile organisms, such as barnacles and mussels, on the rough surfaces of ship hulls results in increased weight and hydrodynamic frictional resistance, accounting for a tremendous increase in fuel consumption, greenhouse gas emissions, dry-docking time, vessel maintenance, and marine transport cost [13,14,15,16,17,18]

Methods

Results

Conclusion