Synthesis And Characterization Of Betulin Fatty Acid Monoester Thiosemicarbazone And Its Metal Complexes

Betulin is widely found in the bark of white birch,and is a natural compound of pentacyclic triterpenes.It has good biological activity,including anti-tumor,anti-HIV,anti-inflammation,quick healing wounds,anti-allergy,liver protection and other functions.It has broad prospects.Carboxylic acid is introduced in the C-3 position of betulin could enhance its anti-HIV activity.The introduction of large electron-absorbing groups in the C-28 position can improve their biological activity,solubility and bioavailability.Thiosemicarbazone is a Schiff base.As a good anti-tumor and anti-bacterial bioactive compound,it has been widely studied.Metal Cu,Ag,Cd and Pd have also been widely reported in the field of anticancer drugs,which make the corresponding compounds better in the compounds,improve their bioavailability,and have better biological activity.In this paper,three series of compounds are designed by using the principle of drug combination.In the series 1,the C-28 hydroxyl group of the betulin was protected by triphenylchloromethane,and its C-3 was introduced to the succinate group,and the protective group was removed from the c-28 position.The c-28 is oxidized into an aldehyde group,which is connected with thiosemicarbazone,and finally is complexed with metal ions.In series 2,the C-28 hydroxyl group of the betulin was introduced to the succinate group,and the C-3 was oxidized into ketone,so that the C-3 ketone carbonyl group was connected with thiosemicarbazone,and finally complexed with the metal ion Cu,Ag,Cd and Pd.The synthesis of series 3 is based on series 2,and the glutarate group is introduced in its Cc-28 position,and its C-3 position is oxidized,and the thiosemicarbazone group is introduced,which is finally complexed with metal ions.The 10 compounds were synthesized by IR,1H-NMR,MALDI-TOF-MS,Elemental analysis,Thermogravimetric analysis,antibacterial activity experiment,cancer cell proliferation experiment analysis and cancer cell protein imprinting.Studies have shown that the complex is complexed in the form of ligand and metal 2:1,and complex in the N and S atoms of the metal.The water solubility and lipid solubility have been greatly improved.The antibacterial activity test and anti-hela cancer cell activity test of the synthesized compounds were found they have a good effect on anti-bacterial and anti-cancer.Among them,28-O-succinylbetulone was a significant antibacterial activity of Streptococcus mu tans 3289bacteria,with the MIC value of 4.The anti-cancer cell proliferation experiment of ligand and its metal complexes showed a significant increase in the activity of metal complexes relative to their ligands,and their IC50 values were between 10 and 25 uM.Ligands and complexes have the ability to fight cancer cells,and the results of protein imprinting test are between 13.84%and 55.68%.