Synthesis And Biological Activity Of Indole 3-Aldehyde And 3-Thiazole Hydrazone Derivatives

As a very important heterocyclic skeleton,indole is one of the most common structural units of synthetic drugs and natural product isolated drugs with a wide range of pharmacological activities.Blood pressure and other aspects have shown great potential.The design,synthesis and biological activity of small molecules containing indole skeletons have become a hot spot in the field of medicinal chemistry to create new drug molecules.In this thesis,the molecular design theory and the splicing principle of drug active fragments are used to introduce biologically active structural fragments into the indole structure.In order to screen novel high-efficiency antibacterial and antioxidant indole derivatives,three series of indole derivatives 2a-2p,3a-3e,4a-4p are designed and synthesized.And these three series of indole derivatives 2a-2p,3a-3e,4a-4p were confirmed by ¹H NMR,¹³C NMR,HRMS characterization,a total of 37 compounds and 35 new compounds have not been reported in the literatures,and the above all 37compounds have no pharmacological activity reported in any literatures before.The results of in vitro antibacterial activity test showed that compound 2g-2p had good antibacterial activity against Shigella flexneri,and the minimum inhibitory concentration（MIC）were 51.91μmol/L,200.76μmol/L,53.08μmol/L,92.37μmol/L,203.35μmol/L,97.24μmol/L,84.59μmol/L,51.11μmol/L,43.78μmol/L,89.43μmol/L,2h and 2i at the concentrations of 200.76μmol/L and 53.08μmol/L,respectively.It has good antibacterial activity against Staphylococcus aureus,Escherichia coli,Clostridium perfringens,Shigella flexneri.Especially for 2h,which is lower than the minimum inhibitory concentration at 309.46μmol/L（100μg/m L）of positive control chloramphenicol can achieve good bacteriostatic effect against Staphylococcus aureus,Escherichia coli,Clostridium perfringens,Salmonella typhimurium and Shigella flexneri.3b-3e has good bacteriostatic effect on Staphylococcus aureus,Escherichia coli and Shigella flexneri,and the MIC values are between 12.22μmol/L to 64.49μmol/L,which are much lower than the positive control drug chloramphenicol.At the low concentration of 15.29μmol/L and 12.22μmol/L,respectively,3d and 3e still have ideal bacteriostatic properties against Bacillus subtilis.The results of the in vitro antioxidant test showed that the IC₅₀ values of DPPH free radical scavenging of compound 3a with a concentration of 75.46μmol/L was significantly lower than 222.96μmol/L of the positive control L-ascorbic acid,shows a very strong DPPH free radical scavenging ability.The IC₅₀ values of DPPH free radical scavenging of compounds 4a-4n and 4p was significantly lower than the positive control L-ascorbic acid,with IC₅₀ values of 104.83μmol/L,104.22μmol/L,97.01μmol/L,118.29μmol/L,93.64μmol/L,113.30μmol/L,88.04μmol/L,83.75μmol/L,85.40μmol/L,82.26μmol/L,96.35μmol/L,84.79μmol/L,91.30μmol/L,141.71μmol/L,112.12μmol/L,respectively,showing an extremely superior DPPH free radical scavenging ability.