Flavonoid Glycosides with a Triazole Moiety for Marine Antifouling Applications: Synthesis and Biological Activity Evaluation

Abstract

Over the last decades, antifouling coatings containing biocidal compounds as active ingredients were used to prevent biofouling, and eco-friendly alternatives are needed. Previous research from our group showed that polymethoxylated chalcones and glycosylated flavones obtained by synthesis displayed antifouling activity with low toxicity. In this work, ten new polymethoxylated flavones and chalcones were synthesized for the first time, including eight with a triazole moiety. Eight known flavones and chalcones were also synthesized and tested in order to construct a quantitative structure-activity relationship (QSAR) model for these compounds. Three different antifouling profiles were found: three compounds (1b, 11a and 11b) exhibited anti-settlement activity against a macrofouling species (Mytilus galloprovincialis), two compounds (6a and 6b) exhibited inhibitory activity against the biofilm-forming marine bacteria Roseobacter litoralis and one compound (7b) exhibited activity against both mussel larvae and microalgae Navicula sp. Hydrogen bonding acceptor ability of the molecule was the most significant descriptor contributing positively to the mussel larvae anti-settlement activity and, in fact, the triazolyl glycosylated chalcone 7b was the most potent compound against this species. The most promising compounds were not toxic to Artemia salina, highlighting the importance of pursuing the development of new synthetic antifouling agents as an ecofriendly and sustainable alternative for the marine industry.

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

“…Compounds 2a and 2b were synthesized and characterized following previously reported methods and 1 H and 13 C NMR data were in accordance with the previously reported [24] and [16,23], respectively.…”

“…For instance, bromotyramine hybrids containing a 1,2,3-triazole ring were described as inhibitors of biofilm formed by marine bacteria [15]. Recently, previous research developed by our group has identified a chalcone glycoside with a 1,2,3-triazole moiety with promising AF activity against macro and microfouling species, without ecotoxicity to a non-target marine organism [16].…”

“…The anti-microalgal activity of the most promising compounds was also evaluated against a benthic marine diatom, Navicula sp., purchased from the Spanish Collection of Algae (BEA), according to the previously reported [16]. Briefly, diatom cells were inoculated in f/2 medium (Sigma) at an initial concentration of 2-4 × 10 6 cells•mL −1 and grown in 96-well flat-bottom microtiter plates for 14 days in continuous light at 20 • C. Navicula sp.…”

Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry

“…Since the biocides currently used in antifouling coatings have proved to be harmful, the search for effective and low toxic antifouling agents is an urgent request [ 38 , 126 ]. In an attempt to develop more environmentally friendly antifouling compounds, Pereira et al (2021) synthesized a series of glycosylated chalcones and flavones conjugated through a triazole ring, through CuAAC reaction [ 127 ]. Compounds were screened for in vivo anti-settlement activity against the macrofouling organism Mytilus galloprovincialis .…”

Antifouling Marine Coatings with a Potentially Safer and Sustainable Synthetic Polyphenolic Derivative

“…Tertiary colonization occurs with the capture of particles and organisms, such as the larvae of marine macro-organisms, including macroalgae, sponges, cnidarians, polychaetes, mollusks, barnacles, bryozoans, and tunicates [ 5 ]. In the last five years, several antifouling (AF) compounds capable of inhibiting the settlement of the macrofouler, Mytilus galloprovincialis (mussel) larvae, were synthesized by some of us [ 6 , 7 , 8 , 9 , 10 , 11 ]. After structure-AF activity relationship studies on several gallic acid derivatives, we recently discovered that N -(2-aminoethyl)-3,4,5-trihydroxybenzamide hydrobromide (GBA26) ( Figure 1 ) exhibited an optimized potency against the larvae settlement of this mussel with higher LC 50 /EC 50 than the previous parent compound and the emerging biocide Econea ® (tralopyril) [ 12 ].…”