Design, synthesis and mechanism research of novel algicide based on bioactive fragments synthesis strategy

The frequency and intensity of harmful cyanobacterial blooms (HCBs) are increasing all over the world, their prevention and control have become a great challenge. In this paper, a series of 1,3,4-thiadiazole thioacetamides (T series) were designed and synthesized as potential algaecides. Among them, the compound T3 showed its best algacidal activity against Synechocystis sp. PCC 6803 (PCC 6803, EC₅₀ = 1.51 μM) and Microcystis aeruginosa FACHB 905 (FACHB905, EC₅₀ = 4.88 μM), which was more effective than the lead compound L1 (PCC6803, EC₅₀ = 7.7 μM; FACHB905, EC₅₀ = 8.8 μM) and the commercially available herbicide prometryn (PCC6803, EC₅₀ = 4.64 μM；FACHB905, EC₅₀ = 6.52 μM). Meanwhile, T3 showed a lower inhibitory activity (EC₅₀ = 12.76 μM) than prometryn (EC₅₀ = 7.98 μM) to Chlorella FACHB1227, indicating that T3 had selective inhibition to prokaryotic algae (PCC6803, FACHB905) and eukaryotic algae (FACHB1227). Furthermore, the algacidal and anti-algae activities of T3 were significantly better than those of prometryn, while the toxicity of zebrafish and human cells was less than prometryn. Electron microscope, physiological, biochemical and metabonomic analysis showed that T3 interfered with light absorption and light conversion during photosynthesis by significantly reducing chlorophyll content, thus inhibited metabolic pathways such as the Calvin cycle and TCA cycle, and eventually led to the cell rupture of cyanobacteria. These results afforded further development of effective and safe algaecides.