Design,Synthesis And Biological Evaluation Of Nucleoside Phosphoramidate Derivatives And Their Probes

In the course of human civilization,viral infections and cancer have killed millions of people worldwide.At the end of 2019,pneumonia caused by Corona Virus Disease 2019(COVID-19)has swept China and the world,which has contributed to the study of antivirals and related vaccines.Among all kinds of antivirals,one of them is a nucleoside analogues,and these compounds are widely used in the fields of antivirus and anticancer.Because early diagnosis is difficult,cancer mortality is very high.It has also been reported that cancer cells have higher levels of reactive oxygen species(ROS)than normal cells.Therefore,it is important to develop new compounds for selective imaging of hypochlorous acid(HOCl)and selective treatment in cancer cells,and to understand the role of HOCl in the pathogenesis of cancer.However,the design and synthesis of this compound is a challenging task,as no compounds has been reported at this time.The design of nucleoside phosphoramidate derivatives is usually based on Pro Tide prodrug technology.This article designs and synthesizes a series of nucleoside phosphoramidate derivatives based on Pro Tide prodrug technology,and this article first designs compounds that combine probes and a series of nucleoside phosphoramidate derivatives,with the hope that these compounds have both the detection of specific substances in cells and a certain therapeutic effect.In this paper,a probe structure for detecting hypochlorous acid is designed based on the structure of 1,8-naphthalimide,and the probe structure and the nucleoside phosphoramide ester derivative structure are linked together by the click reaction,which is future research on nucleoside phosphoramidate derivatives provides new highlights.In the end,six nucleoside phosphoramidate derivatives were selected for anti-tumor(Hep G2)activity evaluation.The results showed that the test compound RGY-1 had a certain inhibitory activity on tumor cells,while the other groups of compounds all showed obvious Antitumor activity.