Design,Synthesis,Structure-Activity Relationship Of Novel Inhibitors Against Candida Albicans FBA?

Candida albicans is the main pathogens of infection nowadays.With the widespread use of azoles,strains resistant of azoles become more and more serious.This situation requires us to change the methods of designing antifungal drugs fundamentally.Class ? fructose-1,6-diphosphate aldolase(FBA-?)is a key regulatory enzyme,which play an important role in the pathway of gluconeogenesis metabolic.As FBA-II only exist in algae,fungi and other lower organisms,while it doesn't exist in human and higher animals.Therefore,the inhibitors which take FBA-? as the target won't have direct impact on the humans and other higher animals.So,FBA-?,as a new "green" target,were attracted widespread attention.Recent studies indicate that C.albicans FBA-II can be used as a potential new target of novel antibacterial and antifungal drugs.In this dissertation,on the basis of N-chromone benzoyl hydrazine compounds,Three inhibitors of leading compounds were designed and synthesized,which is N-(chromone-thiadiazole)benzamides?N-phenyl-N-aroylthioureas?N-benzoylamino-N-benzoylthioureas.Seventy target compounds were synthesized,which forty compounds haven't been reported.By trying different synthetic routes,finally the used synthetic route simplifies the experimental steps and higher yield.All the compounds were characterized by 1H NMR,13C NMR,and MS.The inhibitory activity against Ca-FBA-II is also tested.The compounds,which have potent inhibitory activity against Ca-FBA-?,were regard as the potential inhibitors.Such as IC50 of Ly-2 is 5.8 ?M?IC50 of L66 is 5.3 ?M.Molecular docking was used in this study,in order to learn about the structure-activity relationship of synthesized compounds and Ca-FBA-?,which provides a new way of further modifications.In addition,some compounds were tested the antibacterial activity,and the result is on progress.