Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2′,4′-Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp.

Abstract

A series of novel oxyalkylchalcones substituted with alkyl groups were designed and synthesized, and the antioomycete activity of the series was evaluated in vitro against Saprolegnia strains. All tested O-alkylchalcones were synthesized by means of nucleophilic substitution from the natural compound 2′,4′-dihydroxychalcone (1) and the respective alkyl bromide. The natural chalcone (1) and 10 synthetic oxyalkylchalcones (2–11) were tested against Saprolegnia parasitica and Saprolegnia australis. Among synthetic analogs, 2-hydroxy,4-farnesyloxychalcone (11) showed the most potent activity against Saprolegnia sp., with MIC and MOC values of 125 µg/mL (similar to bronopol at 150 µg/mL) and 175 µg/mL, respectively; however, 2′,4′-dihydroxychalcone (1) was the strongest and most active molecule, with MIC and MOC values of 6.25 µg/mL and 12.5 µg/mL.

Comparative Therapeutic Effects of Natural Compounds Against Saprolegnia spp. (Oomycota) and Amyloodinium ocellatum (Dinophyceae)

“…To our knowledge, the plant derived compounds investigated in this study have never been used before on viable dinospores of A. ocellatum and only 2 ′ ,4 ′ -Dihydroxychalcone was previously tested for Saprolegnia spp. (75). The present investigation showed that, among the compounds tested, Tomatine and 2 ′ ,4 ′ -Dihydroxychalcone have shown to be effective for both parasites.…”

“…Anyway, other experiments are necessary to clarify if A. ocellatum dinospores may be killed by this compound at higher concentrations or if their motility is only temporarily inhibited in the presence of this substance. However, the results obtained by Flores et al (75) with a spores germination inhibition test on S. parasitica and S. australis, suggest that 2 ′ ,4 ′ -Dihydroxychalcone may display dinosporicide activity at concentrations higher than MIC, whereas at lower concentrations it could inhibit the dinospore movements only for a certain period of time. Nevertheless, since there are no published reports on the use of 2 ′ ,4 ′ -Dihydroxychalcone in fish, further researches will be necessary to determine the effects of this compound on fish in the perspective of its application in aquaculture as remedy against fish parasites.…”

“…At 48 h, the MIC50 (MIC that inhibits 50% of growth) of 2 ′ ,4 ′ -Dihydroxychalcone was between 64 and 128 µg/mL, while treatment with 256 µg/mL drastically decreased mycelial growth. This compound was tested also against Saprolegnia by Flores et al (75), showing a 48 h MIC of 6.25 µg/mL. Partially in accord with these authors, our results show that 2 ′ ,4 ′ -Dihydroxychalcone completely inhibited S. parasitica for 48 h and S. delica for 24 h at a concentration of 24.03 µg/mL (0.1 mM), however some mycelial growth was observed starting at 72 h. Conversely, the tests performed on A. ocellatum show that 2 ′ ,4 ′ -Dihydroxychalcone completely inhibited the dinospore motility at the highest concentrations 50 and 25 µg/ml (0.2 and 0.1 mM) after 1 h of incubation, to then being inhibitory till 3.13 µg/ml (0.013 mM) in long term exposure (24 h).…”

“…after 6 days, its possible application in aquaculture should be better investigated in the future. In fact, Flores et al (75) stated that the use of 2 ′ ,4 ′ -Dihydroxychalcone in the hatchery could be cost effective and safe for both workers and environment, representing a good option to replace synthetic compounds in the control of saprolegniosis. Nevertheless, the observations provided by this research are to be considered preliminary.…”

Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin

“…One naturally occurring chalcone, 1 , and seven oxyalkyl derivates, 2 – 8 , were synthesized. The synthetic strategies applied for the synthesis of new chalcones are outlined in Scheme 1 [ 19 , 20 ].…”