Synthesis And Biological Activity Of Schiff Base Derivatives Containing Adamantane Moiety

Drugs with thiosemicarbazone structure have many biological activities,such as antibacterial,anti-tumor,anti-malaria,anti-viral,etc,which have attracted the attention of scientists.Such drugs can block the synthesis of DNA by inhibiting RNR in cells or bacteria to achieve anti-tumor and antibacterial effects.Studies have shown that the introduction of adamantane structure into active small molecules can increase their lipophilicity,thereby changing the permeability of the membrane and improving the activity of the compound.Therefore,using the principle of pharmacophore splicing to synthesize new high-efficiency,low-toxicity anti-tumor and antibacterial drugs has important research value.A series of thiosemicarbazide Schiff base derivatives containing adamantane were designed and synthesized.The intermediate adamantane benzaldehyde 4 was synthesized via Friedel-Crafts alkylation,radical substitution and oxidation of 1-bromoadamantane.Subsequently,the target compound 7a-h were prepared by condensation reaction between the intermediate 4 and thiosemicarbazide derivatives with different substituents.Finally,the structure of the target compounds were characterized by NMR,IR and MS.The CCK-8 experiment was used to test the cytotoxicity of the target compounds on three human tumor cell lines（A549,He La,MCF-7）and normal cell line（HEK-293）.Experiments show that the target compound has a better inhibitory effect on the proliferation of A549 cells,a weaker inhibitory effect on He La cells,and a poorer inhibitory effect on MCF-7 cells.Among them,the IC₅₀of 7f to A549 is 0.55μM,and all compounds are completely non-toxic to normal cells.In order to further study its antibacterial activity,the agar diffusion method was used to test the antibacterial effect of the target compound on Bacillus subtilis and Escherichia coli.Preliminary antibacterial experiment results show that compounds 7f and 7e have higher antibacterial activities against Bacillus subtilis and Escherichia coli,respectively.Taking into account the results of anti-cancer and antibacterial experiments,compound 7f can effectively inhibit the proliferation of A549 cells and inhibit the growth of bacteria.Therefore,compounds of this type of structure have further research value.