Chemical Structural Modification Of Daidzein And Their Biological Activity

In the last decade,more and more attention has been focused on daidzein and its derivatives.Daidzein and its derivatives possess a wide range of biological activities.To improve the water solubility of daidzein and its derivatives by structural modification is important.To synthesis water-soluble daidzein derivatives and test their biological activity is worthy of careful study.There are great realistic meaning and practical value by explored them.Seventeen daidzein derivatives were synthesized by Mannich reaction,Williamson reaction,sulfonation reaction and Friedel-Crafts acylation.Among them eleven derivatives had not been reported.Synthetic route was as follows:?1?Daidzein was reacted with dimethylamine,diethylamine,dipropylamine,dibutylamine and morpholine respectively.And then 5 Mannich base derivatives?CHL6:8-??dimethylamino?methyl?-4',7-bishydroxy-isoflavone-3'-sulfonic acid;CHL7:8-??diethylamino?methyl?-4',7-bishydroxy-isoflavone-3'-sulfonic acid;CHL8:8-??dipropylamino?methyl?-4',7-bishydroxy-isoflavone-3'-sulfonic acid;CHL9:8-??dibutylamino?methyl?-4',7-bishydroxy-isoflavone-3'-sulfonic acid;CHL10:8-?morpholinomethyl?-4',7-bishydroxy-isoflavone-3'-sulfonic acid?was obtained by sulfonation reaction.?2?Sodium 4',7-bishydroxy-isoflavone-3'-sulfonate was reacted with 4-?aminomethyl?benzoic acid,6-aminohexanoic acid and Tranexamc acid respectively to obtain 3 Mannich base derivatives with novel structure?CHL12:sodium 8-???4"-carboxybenzyl?amino?methyl?-4',7-bishydroxy-isoflavone-3 '-sulfonate;CHL13:sodium 8-???5"-carboxypentyl?amino?methy l?-4',7-bishy droxy-isoflavone-3 '-sulfonate;CHL14:sodium 8-????4"-carboxycyclohexyl?methyl?amino?methyl?-4',7-bishydroxy-isoflavone-3'-sulfonate?.?3?Sodium 4',7-bishydroxy-isoflavone-3'-sulfonate was reacted with ethyl 2-chloroacetate to obtain a new compound?CHL15:potassium 4,,7-bis?ethyl acetatoxy?isoflavone-3'-sulfonate?.?4?Daidzein was reacted with succinic anhydride,glutaric anhydride respectively to synthesize 2 derivatives with carboxylic acid group?CHL16:4"-oxo-4"-?4',7-bishydroxy-isoflavone-3'-yl?butanoic acid;CHL17:5"-oxo-5"-?4',7-bishydroxy-isoflavone-3'-yl?pentanoic acid?.These derivatives were characterized by IR,1H-NMR,13C-NMR,135°DEPT,ESI-MS,X-ray diffraction.CHL6,CHL7,CHL8,CHL9,CHL10,CHL12,CHL13,CH114,CHL16,CHL17 can be changed into sodium salts for good water solubility.Some daidzein derivatives were investigated by thermal gravimetric analysis.The plasma recalcification time of some daidzein derivatives was obtained at different concentrations.Isothermal titration calorimetry?ITC?was applied to investigate the interaction between sodium 4',7-bishydroxy-isoflavone-3'-sulfonate and human serum albumin?HSA?in the buffer solution.The thermodynamic parameters?N,KD,?H,and ?S?were calculated by ITC:N=0.927,K_D=7.51×10^-4 M^-1,?H=-3115 cal/mol,AS=11.9 cal/mol/K.