The Research Of Structure-activity Relationship Of Photosensitizers And PI3K Anti-tumor Drug Discovery

Photodynamic therapy was first appeared in the 1950 s.It is a new type of treatment(including diagnosis and treatment)for the treat of tumor and non-neoplastic diseases.Nowadays,photodynamic therapy has been widely used in various clinical fields.The prospects are very broad.As an important core of photodynamic therapy,photosensitizers have become the target of reform,development and innovation by the researchers for their safety problems and high prices.In this paper,the related literatures of various photosensitizers are collected,and the relevant characteristic data of photosensitizers are extracted.The purpose of this paper is to study the relationship between photosensitizer structure and its singlet oxygen yield,and establish a corresponding classification model,which is also used for subsequent photosensitivity.The development of the agent provides a scientific theoretical basis.Cancer is becoming the second disease threat to human health worldwide.Traditional anti-cancer agents,which directly interfere with mitosis,DNA synthesis and repair systems,are often connected with drawbacks such as low efficiency and high toxicity.A number of key signaling pathways,which play an important role in tumorigenesis and cancer development,have been identified.Thereafter,smallmolecular inhibitors specifically targeting these key molecules become new class of anti-cancer agents,providing one of the main opportunities to overcome human cancers.A series of thieno[3,2-d]pyrimidine derivatives as phosphatidylinositol 3-kinase(PI3K)inhibitors was designed using the combination strategy.The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3 K,culminating in the discovery of 7 and 21.Determination of a co-crystal structure of 7 complexed with PI3Kα provided the structural basis for the high enzymatic activity.Furthermore,cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mTOR pathway.The results provided potent simplified inhibitors of PI3 K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.