Structure-Based Design and Synthesis of Novel Dual-target inhibitors against Cyanobacterial Fructose

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  Cyanobacteria harmful algal blooms (HABs) pose an increasingly serious water pollution problem all over the world.Class Ⅱ Fructose-l,6-bisphoshate aldolase (Cy-FBA-Ⅱ) and cyanobacteria Fructose-l,6-Bisphosphatase (Cy-FBPase) are two neighbouring key regulatory enzymes in Calvin cycle of cyanobacteria photosynthesis system.Each of them might be taken as the potential target for designing novel inhibitors to chemically control harmful algal blooms (HABs).In the present paper, a series of novel inhibitors were designed, synthesized and optimized based upon the structural and interactional information of both Cy-FBA-Ⅱ and Cy-FBPase, and their inhibitory activities were examined in vitro and in vivo.The experimental results showed that compounds L20a-L20d exhibited high Cy-FBA-Ⅱ inhibitory activity (IC50 =2.3-5.7 μM) and moderate Cy-FBPase inhibitory activity (IC50 =92.0-140.1 μM), however, compounds L20e-L20h could potentially inhibit both of Cy-FBA-Ⅱ and Cy-FBPase with IC50 values less than 30 μM, which demonstrate more or less dual-target inhibitors feature.Moreover, most of them exhibited high algicide activity (EC50 =0.8-15.3 ppm) against cyanobacteria Synechocystis sp.PCC 6803.
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