Synthesis,Antitumor Activity And Interaction With Bovine Serum Albumin Of Genistein Derivatives

Object:To synthesize a series of novel genistein amino acid ester derivatives,and to study the antitumor activity of the genistein derivatives and the interaction with bovine serum albumin.Methods:A series of genistein amino acid ester derivatives were obtained by substitution,hydrolysis and condensation reaction with genistein as the mother core and the structure is confirmed by ¹H NMR spectra,¹³C NMR spectra,mass spectrum.;The antiproliferative effect of genistein amino acid ester derivatives on tumor cells was determined by MTT assay;The cell division cycle and apoptosis effect of genistein amino acid ester derivatives on tumor cells was determined by flow cytometry;Determination of quenching type,binding constant and binding force in the interaction between compounds and bovine serum albumin?BSA?by fluorescence quenching spectroscopy;UV-visible absorption spectroscopy,simultaneous fluorescence,three-dimensional fluorescence,circular dichroism spectroscopy,molecular docking were used to study of changes in BSA conformation after binding of compounds to BSA.Results:33 genistein amino acid ester derivatives were synthesized.The results of MTT assay showed that most of the target compounds had good anti-tumor cell proliferation activity compared with genistein.Among them,compound 8j had the strongest anti-proliferative activity against colorectal cancer HCT-116 cells(IC₅₀=2.76?M).Flow cytometry results showed that compound 8j could block colorectal cancer HCT-116cell division in G1 phase and also induce apoptosis of colorectal cancer HCT-116 cells.The interaction between compound and BSA showed that the combination of genistein and its derivatives 7a,7b,7c,7l and BSA is a static quenching process and a spontaneous process.The main forces are hydrogen bonding and van der Waals forces.The binding constants of derivatives 7a,7b,7c,7l were both greater than the binding constants of genistein and BSA.In addition,conformational studies such as UV-Vis spectroscopy and circular dichroism spectroscopy indicated that the combination of genistein and its derivatives 7a,7b,7c,7l and BSA can change the microenvironment of BSA molecular residues and the?-helix content of BSA molecules.Conclusion:?1?A total of 33 genistein amino acid ester derivatives were synthesized.?2?Most of the 33 genistein amino acid ester derivatives synthesized have good anti-tumor cell proliferation activity,and compound 8j has the strongest anti-colorectal cancer HCT-116 cell proliferation activity.?3?The genistein amino acid ester derivatives?7a,7b,7c,7l?have greater binding capacity to BSA than genistein.In addition,the binding of the genistein amino acid ester derivative?7a,7b,7c,7l?to BSA reduces the hydrophobicity and?-helix content of the BSA,thereby changing the conformation of BSA.