Novel Algicides against Bloom-Forming Cyanobacteria from Allelochemicals: Design, Synthesis, Bioassay, and 3D-QSAR Study.

Abstract

Simple SummaryDue to the frequent outbreaks of cyanobacteria bloom worldwide, research on novel algicides has attracted more and more attention. At present, allelochemicals have been reported as promising natural algicides. However, current studies mainly focus on the parent compounds, and the structural modification of original allelochemicals has been rarely involved. In this study, phenolic acid derivatives were innovatively synthesized as potential algicides, and lead compounds with excellent activity were found. For instance, upon the algicidal activity on Aphanizomenon flos-aquae, the EC50 of the best active compound 18 reached 0.63 µM (0.17 mg/L), while the EC50 values of previously reported allelochemicals have been basically at the mg/L level. The result indicates that the algicides reported in this study are more efficient at inhibiting cyanobacteria with lower effective concentrations than most previously reported compounds. Moreover, 3D-QSAR models were constructed and provided a theoretical guidance for further structure optimization of compounds to achieve better algicidal activity.Cyanobacteria bloom caused by water eutrophication has threatened human health and become a global environmental problem. To develop green algicides with strong specificity and high efficiency, three series of ester and amide derivatives from parent allelochemicals of caffeic acid (CA), cinnamic acid (CIA), and 3-hydroxyl-2-naphthoic acid (HNA) were designed and synthesized. Their inhibitory effects on the growth of five harmful cyanobacterial species, Microcystis aeruginosa (M. aeruginosa), Microcystis wesenbergii (M. wesenbergii), Microcystis flos-aquae (M. flos-aquae), Aphanizomenon flos-aquae (Ap. flos-aquae), and Anabaena flos-aquae (An. flos-aquae), were evaluated. The results revealed that CIA esters synthesized by cinnamic acid and fatty alcohols showed the best inhibition effect, with EC50 values ranging from 0.63 to >100 µM. Moreover, some CIA esters exhibited a good selectivity in inhibiting cyanobacteria. For example, the inhibitory activity of naphthalen-2-yl cinnamate was much stronger on Ap. flos-aquae (EC50 = 0.63 µM) than other species (EC50 > 10 µM). Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis was performed and the results showed that the steric hindrance of the compounds influenced the algicidal activity. Further mechanism study found that the inhibition of CIA esters on the growth of M. aeruginosa might be related to the accumulation of malondialdehyde (MDA).