Synthesis And Biological Evaluation Of The Derivatives Of KP372-1

NAD(P)H: Quinone Oxidoreductase 1(NQO1)is a very attractive target for cancer therapy.A number of compounds targeting NQO1 have been synthesized and studied by chemists and biologists in recent years,some of which have entered the stage of clinical research.This thesis mainly studied the synthesis and biological evaluation of the derivatives of KP372-1.Firstly,the overview of NQO1 and the development of NQO1 targeting compounds in recent years were summarized.Secondly,a series of derivatives of KP372-1 were synthesized from 5-hydroxy-1 ketene by alkylation reaction,tin dioxide oxidation,and finally reacting with(1,2,3,4)-tetrazole-1,5-diamine.Then its biological evaluation on A549(human non-small cell lung cancer cells)were tested and most compounds could completely kill cancer cells in the micromolar concentration range.Unfortunately,most compounds might act on other reductases,such as thioredoxin reductase or P-450 R reductase rather than NQO1.Finally,synthesis of PROTAC(proteolysis targeting chimeras)targeting NQO1 were attempted.The synthetic study will provide a route for further research work towards NQO1.