Design, Synthesis, and Mode of Action of Thioacetamide Derivatives as the Algicide Candidate Based on Active Substructure Splicing Strategy.

Lakes and reservoirs worldwide are experiencing a growing problem with harmful cyanobacterial blooms (HCBs), which have significant implications for ecosystem health and water quality. Algaecide is an effective way to control HCBs effectively. In this study, we applied an active substructure splicing strategy for rapid discovery of algicides. Through this strategy, we first optimized the structure of the lead compound , designed and synthesized three series of thioacetamide derivatives (series , , ), and then evaluated their algicidal activities. Finally, compound with excellent performance was found, which accelerated the process of discovering and developing new algicides. The biological activity assay data showed that had a significant inhibitory effect on FACHB905 (EC = 0.46 μM) and sp. PCC6803 (EC = 0.95 μM), which was better than the commercial algicide prometryn (. FACHB905, EC = 6.52 μM; sp. PCC6803, EC = 4.64 μM) as well as better than lead compound (. FACHB905, EC = 8.80 μM; sp. PCC6803, EC = 7.70 μM). The relationship between the surface electrostatic potential, chemical reactivity, and global electrophilicity of the compounds and their activities was discussed by density functional theory (DFT). Physiological and biochemical studies have shown that might affect the photosynthesis pathway and antioxidant system in cyanobacteria, resulting in the morphological changes of cyanobacterial cells. Our work demonstrated that might be a promising candidate for the development of novel algicides and provided a new active skeleton for the development of subsequent chemical algicides.