Synthesis And Antitumor Activity Of Novel Schiff Base Derivatives Containing Adamantane Skeleton

Adamantane frameworks are widely used in anticancer and antiviral drugs due to their excellent physical and chemical properties.Schiff base derivatives have various biological activities,such as antibacterial,anti-tumor,etc.In recent years,these compounds have attracted widespread attention from pharmaceutical researchers.Research has shown that introducing active small molecules into the adamantane structure can increase its lipophilicity,thereby altering the permeability of the drug membrane and significantly improving its biological activity.This article combines the adamantane skeleton and Schiff base structural units to obtain efficient and low toxicity anticancer small molecules.Firstly,a series of novel Schiff base derivatives containing adamantane frameworks were designed and synthesized using 1-bromadamantane as the starting material.An important intermediate compound 5was obtained through Friedel Craftsalkylation,radical substitution,oxidation,and demethylation reactions.Subsequently,the intermediate was condensed with different thiosemicarbazide derivatives with different substituents to synthesize the first type of target compound 7a-h;This intermediate compound also reacts with aniline with different substituents to obtain a second type of target compound 9a-h.Structural characterization of the target compound was carried out through nuclear magnetic resonance,infrared spectroscopy,and mass spectrometry.Finally,using 5-fluorouracil as a positive control,ADMET was used to preliminarily predict the drug like and pharmacokinetic properties of the target compound;In addition,CCK-8 was used to detect the toxicity of the target compound on three types of cancer cells A549,He La,MCF-7,and a normal human embryonic kidney cell Hek-293.The experimental results showed that the first type of target compound 7g had the best inhibitory activity on He La and MCF-7,but all compounds had unsatisfactory inhibitory effects on A549;The second type of target compound 9d has the best inhibitory activity on He La cells,while all compounds have lower inhibitory rates on A549 and MCF-7.In addition,all target compounds have no cytotoxicity to normal cells.Therefore,using the splicing principle of pharmacophore to synthesize new low toxicity,high efficiency anticancer drug small molecules has potential application value in the field of anticancer research.