Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents

Abstract

Marine biofouling is a natural process that represents major economic, environmental, and health concerns. Some booster biocides have been used in biofouling control, however, they were found to accumulate in environmental compartments, showing negative effects on marine organisms. Therefore, it is urgent to develop new eco-friendly alternatives. Phenyl ketones, such as benzophenones and acetophenones, have been described as modulators of several biological activities, including antifouling activity (AF). In this work, acetophenones were combined with other chemical substrates through a 1,2,3-triazole ring, a strategy commonly used in Medicinal Chemistry. In our approach, a library of 14 new acetophenone–triazole hybrids was obtained through the copper(I)-catalyzed alkyne-azide cycloaddition “click” reaction. All of the synthesized compounds were evaluated against the settlement of a representative macrofouling species, Mytilus galloprovincialis, as well as on biofilm-forming marine microorganisms, including bacteria and fungi. The growth of the microalgae Navicula sp. was also evaluated after exposure to the most promising compounds. While compounds 6a, 7a, and 9a caused significant inhibition of the settlement of mussel larvae, compounds 3b, 4b, and 7b were able to inhibit Roseobacter litoralis bacterial biofilm growth. Interestingly, acetophenone 7a displayed activity against both mussel larvae and the microalgae Navicula sp., suggesting a complementary action of this compound against macro- and microfouling species. The most potent compounds (6a, 7a, and 9a) also showed to be less toxic to the non-target species Artemia salina than the biocide Econea®. Regarding both AF potency and ecotoxicity activity evaluation, acetophenones 7a and 9a were put forward in this work as promising eco-friendly AF agents.

Novel metabolite madeirone and neomarinone extracted from Streptomyces aculeoletus as marine antibiofilm and antifouling agents

“…This napyradiomycins displayed settlement results of M. galloprovincialis larvae with an EC 50 of less than 5 μg/mL and a LC 50 /EC 50 ratio greater than 15 (Pereira et al, 2020). Further, the EC 50 of (2) was lower than that of other synthesized compounds or compounds from distinct bioresources (Neves et al, 2021;Pereira et al, 2021;Resende et al, 2021).…”

Chemical synthesis and antifouling activity of monoterpene–furan hybrid molecules

“…Therefore, we have designed monoterpene–furan hybrid molecules 4 , in which the structural variety is introduced in the monoterpene unit, as novel antifoulants in this study. 22–24 Herein, we report the concise synthesis of nine hybrids 4a–4i , and their antifouling activity and toxicity toward the cypris larvae of the barnacle Balanus ( Amphibalanus ) amphitrite .…”