Design?Synthesis And Biological Activity Research On Indole Diketonepiperzaine Derivatives

The modification of natural bioactive products has been an important way of drug discovery.Indole diketopiperazine derivatives are widely distributed in nature,especially as the secondary metabolites of microorganisms.It has a wide variety of biological activity for possessing both indole and diketopiperazine pharmcophore.Bervianamide F,an indole diketopiperazine compound from the secondary metabolites of aspergillus,as biosynthesis precursor microbes in a variety of good bioactive natural products.In previous studies,we found that the compound has potent allelopathic activity,so futher research will be carried out.By the technology of computer-aided drug design,Twenty target compounds were synthesized including lead compounds bervianamide F,5-Br-bervianamide F and eighteen bervianamide F derivatives whose pyrrole ring are replaced.All novel synthetic compounds are verified by GC-MS,¹HNMR,¹³CNMR spectroscopy methods.A concise and effective synthetic route was exploited.by a pot method to get the target compounds which greatly shortens the reaction steps and the reaction time.All the compounds were tested against TIR1,anti-phytopathogenic fungi and allelopathic activity.The results showed that the compounds do not have TIR1inihibiton;At 50?M concentration,bervianamide F exhibited Farium sulphureum inhibition activity with a inhibition rate of 63.41%.2.1 b exhibited Farium sulphureumand and Colletotrichum gloeosporiodes inhibition with a inhibition rate of62.57%,51.31%.The inhibition rate of 2.3 h against Farium sulphureum was 49.34%;Allelopathic activity test results showed that all compounds exhibitweed roots inhibition.The compound 2.2e,2.3a can inhibit the growth of lettuce and weed,have an stem index?RI?comparable with positive control of glyphosate.Above all,we use the technology of computer-aided drug design to synthesize a serious of indole diketopiperazine derivatives,and explore a concise synthetic routeThebiological assay indicated two compounds has good allelopathic activity which have the potential to become a novel potent herbicides.