Structure Modification Of Genistein And Blood Physiological Activity Research

Genistein are widely found in nature,possess much biological activities,which were extensively used in the fields of pharmacy,health products,and so on.However,genistein and the derivative drug have not been found in the clinical,because of the poor amphipathic and first pass effect.Therefore,it is a very important objective to develop more genistein derivatives that have high pharmacological activity and high bioavailability.To improve the genistein disadvantages,synthetic route was been designed as follows:(1)To introduct amino or carboxyl,genistein was reacted with primary amine,secondary amine,p-aminomethyl beozoic acid and tranexamic acid through Mannich reaction(2)The sulfonated derivatives of genistein were obtained by sulfonation reaction.(3)Esterified derivatives of genistein were synthesized through the reaction of genistein with p-aminomethyl beozoic acid and tranexamic acid which were reacted with phthalic anhydride.The synthetic conditions and purification methods were determined after long-term exploration.The twenty genistein derivatives were characterized by IR,ESI-MS,1H-NMR and 13C-NMR.Sixteen derivatives have not been reported.Parts of activity determinations of the products have been studied.The detail as following:(1)The interaction between genistein sulfonated derivatives and human serum albumin(HSA)was studied using UV-Vis absorption spectroscopy and fluorescence spectroscopy.The experimental results indicated that the derivatives effectively quenched the intrinsic fluorescence of HSA via a static quenching process.And the hydrogen bonding and van der Waal's forces were the predominant intermolecular forces and situated in Site I.(2)The AutoDock has been used to study the interaction between genistein derivatives and HSA.The results showed that the derivatives are more easily interact with HSA spontaneously and situated in Site I of HSA.The way of genistein derivatives act with protein residues were studied by LigPlot+.(3)The blood actives were speculated by virtual screening.Then the blood actives were tested through the measurements of plasma recalcification and coagulation four indices.