Design Of A New Synthon Of Chromone And Synthesis Of Its Diverse Skeleton Compounds And Their Biological Activities

Cancer is a global public health problem.At present,the problem of large toxic and side effects of antitumor drugs is common.Therefore,the search for antitumor drugs with little toxic and side effects is the direction of global scientists’ efforts.Through unremitting research,it is found that most compounds with natural product skeletons show good antitumor activity,and compounds with chromone skeletons are one of the focuses of people’s research.Therefore,modifying and modifying the backbone structure of natural products is an important way to discover certain biologically active compounds.In this thesis,a series of pyrazolinone compounds with chromone skeletons are constructed by Knoevenagel condensation reaction based on the active framework transition and splicing principles of new drug design,and a series of chromones are synthesized by the Michael/Michael cycloaddition reaction.The pyrazolinone chalcone compounds of the skeleton were then synthesized,and the polycyclic pyrrolopyronospiro-epoxidized indole compounds with a chromone skeleton were synthesized.Finally,the antitumor activity of the synthesized compounds was evaluated in vitro.The first part of the work is the synthesis of pyrazolinone chalcone compounds containing a chromone skeleton.Through the two-step reaction of Knoevenagel condensation and Michael/Michael cycloaddition,the pyrazolinone chalcones containing a chromone skeleton were successfully constructed.For the compound,the reaction route was determined by screening the reaction conditions,and a high yield(76%-98%)was obtained.The diastereoselectivity was as high as dr ? 20: 1.This reaction route is economical and efficient,and also provides a method for constructing pyrazolinone chalcone compounds containing a chromone skeleton.The second part is the synthesis of polycyclic pyrrolidine spiro-epoxidized indole compounds containing a chromone skeleton.The two-step reaction of knoevenagel condensation and 1,3-dipolar cycloaddition successfully constructed a polycyclic ring containing a chromone skeleton.Pyrrolidine spiro-epoxidized indole compounds were obtained in a yield of 61% and had diastereoselectivity greater than 4: 1.The third part is to evaluate the antitumor activity of the synthesized compounds in vitro.The MTT method was used to study the anti-tumor activity of 45 synthetic chromone pyrazolinone chalcone compounds in vitro using cisplatin,a commonly used anticancer drug as a positive control,to investigate its human chronic myeloid leukemia cells K562 cells.Inhibitory effect of strains.The results showed that compounds 3b,3c,3g,3l,3m,3s,3t,3ac,and 3ar had good inhibitory activities on K562.Among them,3b and 3l were close to the positive control drug cisplatin,showing potential research value.These 10 compounds were then tested for cytotoxicity to normal mouse L929 cell lines,and the results showed that these compounds had lower inhibitory activity on human normal cells,and the cytotoxicity was lower than the positive control drug cisplatin.