Design,Synthesis and Toxicity on HepG2 Cells of Derivatives Based on the Structure of Genipin
Objective:To design and synthesize a series of iridoid derivatives based on the structure of genipin,and to investigate their toxic effects on HepG2 cells,in order to provide theoretical guidance for the search of hepatoprotective drugs.Methods:The SN1 substitution reaction was performed with low carbon alcohols(methanol,ethanol,n-propanol,isopropanol,n-butanol,t-butanol)in low temperature anhydrous and anaerobic system using genipin as starting material and boron trifluoride ether as catalyst.The structure of the products were characterized by 1H-NMR.The cytotoxicity of the compounds to HepG2 cells were evaluated by CCK-8 method.Glutathione was used as a positive control and IC50 was used to indicate its toxicity.Results:Six genipin derivatives were designed and synthesized,which were 1-O-methyl genipin,1-O-ethyl genipin,1-O-n-propyl genipin,1-O-isopropyl genipin,1-O-n-butyl genipin,1-O-t-butyl genipin.Their structures were correctly characterized by 1H-NMR.The IC50 of glutathione was greater than 1 000 μmol/L,the IC50 of genipin was(558.70±22.81)μmol/L,and the IC50 of 1-O-n-propyl genipin and 1-O-n-butyl genipin were(537.40±188.10)μmol/L and(586.10±42.41)μmol/L,respectively.The cytotoxicity was lower than that of glutathione,but similar to that of genipin.The IC50 value of 1-O-isopropyl genipin was(628.30±38.72)μmnol/L,which was lower than that of glutathione and higher than that of genipin.The IC50 values of 1-O-methyl genipin,1 O-ethyl genipin and 1-O-t-butanol genipin were as follows:(324.30±55.67)μmol/L,(111.95±18.06)μmol/L,(91.10±15.20)μmol/L,which were lower than glutathione and genipin.Conclusion:Six genipin derivatives were synthesized.A simple and controllable method for the synthesis of genipin derivatives was obtained.Among them,genipin derivatives 1-O-n-propyl genipin,1-O-isopropyl genipin and 1-O-n-butyl genipin were less toxic to HepG2 cells.
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