Synthesis And Optimization Of Novel Target Inhibitors Against Cyanobacteria And Candida Albicans Fructose-1,6-Bisphosphate Aldolase

Type Ⅱ fructose-1,6-diphosphate aldolase(FBA-Ⅱ)is a key regulatory enzyme in glycolysis and gluconeogenesis pathway.If FBA-II activity was inhibited,in vivo glu-cose metabolism pathway can be blocked,thus achieving suppression growth or killing effect.Cyanobacteria FBA-II and Candida albicans FBA-II has been shown as a design appropriate algaecide and bactericide potential targets.In the previous study,our group used virtual screening techniques on Cyanobacteria and Candida albicans FBA-II,successfully screened a hit compoumd CFL-22 with a good inhibitory activity.As a precursor compound,CFL-22 was modified and trans-formed into four series of compounds.All synthesizied compounds were characterized by NMR and mass spectra.Their biological activity was also tested.The series Ⅰβ-subunit substituted phenylhydrazine-α,γ-dicarbonyl compounds has 45 compounds;the series II phenylhydrazone compounds has 16 compounds;the series III benzoyl hydrazone com-pounds has 17 compounds,and the series Ⅳ N-(substituted imide)benzamide com-pounds has 36 compounds.The compounds of series I were tested on Cyanobacteria and Candida albicans FBA-II,and the results of the biological activity showed that between the series I there are 11 compounds which exhibit 70%inhibition rate against Candida albicans FBA-II at 50 μM.The best effective compound is I-28,whose inhibition rate reached 95.6%at 50μM,IC50 = 12.3 ± 0.9 μM.There are 7 compounds which exhibit 70%inhibition rate against cyanobacteria FBA-II at 50μM,and the best effective compound is I-31,whose inhibition rate reached 95.5%at 50 μM.The compounds of series Ⅱ and series Ⅲ were tested on Candida albicans FBA-Ⅱ,and the results of the biological activity showed that between the series II there are 11 compounds which exhibit 80%inhibition rate against Candida albicans FBA-Ⅱ at 50 μM.The best effective compound is Ⅱ-8,whose inhibition rate reached 100.9%at 50 μM,IC50 = 2.7 ± 0.2 μM.Between the series 6 there are 11 compounds which exhibit 60%inhibition rate against Candida albicans FBA-II at 50 μM.The best effective compound is Ⅲ-6,whose inhibition rate reached 91.1%at 50 μM,IC50=5.5±1.2μM.The compounds of series IV were tested on Cyanobacteria FBA-II,and the results of the biological activity showed that between the series IV there are 22 compounds which exhibit 70%inhibition rate against Cyanobacteria FBA-Ⅱ at 50 pM and there are 19 compounds whose IC50 is less than 10 μM.There are 11 compounds whose EC50 is less than 10 ppm against Cyanobacteria algae.The best active compound is Ⅳ-10,which IC50 = 1.7± 0.5 μM,EC50 = 0.6±0.1ppm.