From Natural Xanthones to Synthetic C-1 Aminated 3,4-Dioxygenated Xanthones as Optimized Antifouling Agents.

Emília Sousa,Marta Correia-Da-Silva,Stefan Clerens,Ancy Thomas,Agostinho Lemos,Sandra Pereira,Vitor Vasconcelos,Jeffrey E Plowman,Alexandre Campos,Joana R Almeida,Diana I S P Resende,Madalena Pinto

doi:10.3390/md19110638

Emília Sousa, Marta Correia-Da-Silva + Show 10 more

Open Access

https://doi.org/10.3390/md19110638

Copy DOI

Abstract

Biofouling, which occurs when certain marine species attach and accumulate in artificial submerged structures, represents a serious economic and environmental issue worldwide. The discovery of new non-toxic and eco-friendly antifouling systems to control or prevent biofouling is, therefore, a practical and urgent need. In this work, the antifouling activity of a series of 24 xanthones, with chemical similarities to natural products, was exploited. Nine (1, 2, 4, 6, 8, 16, 19, 21, and 23) of the tested xanthones presented highly significant anti-settlement responses at 50 μM against the settlement of mussel Mytilus galloprovincialis larvae and low toxicity to this macrofouling species. Xanthones 21 and 23 emerged as the most effective larval settlement inhibitors (EC50 = 7.28 and 3.57 µM, respectively). Additionally, xanthone 23 exhibited a therapeutic ratio (LC50/EC50) > 15, as required by the US Navy program attesting its suitability as natural antifouling agents. From the nine tested xanthones, none of the compounds were found to significantly inhibit the growth of the marine biofilm-forming bacterial strains tested. Xanthones 4, 6, 8, 16, 19, 21, and 23 were found to be non-toxic to the marine non-target species Artemia salina (<10% mortality at 50 μM). Insights on the antifouling mode of action of the hit xanthones 21 and 23 suggest that these two compounds affected similar molecular targets and cellular processes in mussel larvae, including that related to mussel adhesion capacity. This work exposes for the first time the relevance of C-1 aminated xanthones with a 3,4-dioxygenated pattern of substitution as new non-toxic products to prevent marine biofouling.

Highlights

Marine biofouling, a process in which submerged surfaces are colonized by micro-and macro-organisms, has been an increasingly serious problem to several industrial sectors around the world, causing vast economic losses and increasing security risks [1]
In an an attempt attempt to to further further explore explore the the potential potentialof ofxanthone xanthonederivatives derivativesfor forantifouling antifouling purposes, we explored for the first time the antifouling activity of a series of nineteen synpurposes, we explored for the first time the antifouling activity of a series of nineteen thetic analogs
Four distinct approaches were developed a aromatic heterocyclic with a dibenzo-γ-pyrone optimizedXanthones over theare last years oxygenated toward the synthesismolecules, of this scaffold

Summary

Introduction

A process in which submerged surfaces are colonized by micro-and macro-organisms, has been an increasingly serious problem to several industrial sectors around the world, causing vast economic losses and increasing security risks [1]. For the shipping industry, the attachment of marine organisms on ship hulls causes decreased speed performance, leading to increasing fuel consumption and pollution [2]. Parof 16 ticularly for the shipping industry, the attachment of marine organisms on ship 2hulls causes decreased speed performance, leading to increasing fuel consumption and pollution [2]. Biofouling harmful effects are extendable to the environment and, toto human health

Methods

Results

Conclusion