Design,Synthesis And Antitumor,Antioxidant Activities Of Baicalein Derivatives And Synthesis And Characterization Of Novel Bicyclic Lactam-Based Fluorescent Probe

Part 1: Design,synthesis and antitumor,antioxidant activities of baicalein derivativesObjective A series of flavonoids derivatives were designed and synthesized,and lead compounds with excellent biological activity were screened.Methods The flavonoids were used as basic nucleus to carry out the structural modification.Three kinds of flavonoid derivatives and a 3-hydroxypyridin-4-one derivative were designed and synthesized.The structures were characterized by 1H NMR and 13 C NMR.DPPH and ABTS were used to detect the antioxidant and free radical scavenging activities of the target compounds.MTT method was used to detect the anti-tumor activities.Results Seven target compounds were successfully synthesized.Compounds 5 and 6have great antioxidant and radical scavenging activities.Compounds 2,6,7 have relatively great anti-tumor activities.Conclusion Compounds 5 and 6 of which the ring C is a furan ring have excellent antioxidant activities.The number of hydroxyl substituents and the position of substitution in the structure have an important influence on the antioxidation and free radical scavenging abilities of the compounds.The results of antitumor experiments indicate that the structure of the flavonoids still has a large room for improvement.Part 2: Synthesis and characterization of novel bicyclic lactam-based fluorescent probeObjective To detect intracellular labile iron and remove excess iron,a novel fluorescent probe based on bicyclic lactam is designed and synthetized.The probe exhibits high sensitivity and selectivity towards Fe3+ and Fe2+.The ester functional group of the probe can be hydrolyzed by the related esterase in cells,and the log P values of this molecule and its hydrolyzed analogue are-0.16 and-0.80,respectively.Methods The synthesis of a novel bicyclic lactam-based fluorescent probe is described,where the chelator function merges with the fluorescent entity.3-hydroxypridin-4-ones act as the chelator function and the probe is modified by adding an ester which can be hydrolyzed by the esterase in the cell,and the released carboxyl group can prevent the probe penetrating from the cell.log P was measured by shake flask method.Results The logP values of the probe and its hydrolyzed analogue are-0.16 and-0.80,respectively.With an increase of Fe(III)concentration,the fluorescence of the probe gradually decreased,the other metal ions have no significant influence to the probe.Conclusion The probe exhibits high sensitivity and selectivity towards Fe(III).The suitable log P values of the probe and its hydrolysate make it realizable for the ligand to remain in cells to chelate labile iron.