Design,Synthesis And Biological Activity Of β-Carboline N-Fused Triazole Derivatives

β-Carboline alkaloids come from a wide range of sources,not only can be extracted from natural products,but also exist in many mammals,herbs,marine organisms,microorganisms,etc.,and can also be synthesized by chemical methods.β-carboline alkaloids are important basic nitrogen-containing heterocyclic compounds,which contain an inert skeleton of a pyridine ring.It is precisely because of this special structure that it exhibits a wide range of pharmacological and biochemical activities,including sedative,antitumor,antibacterial,antiviral,antimalarial,and antipsychotic activities.As important nitrogen-rich heterocyclic compounds,1,2,3-triazole compounds have a wide range of applications in biology,medicine,and materials,and have good performance in antibacterial,anticancer,antiviral,and antituberculosis.Based on previous literature reports and laboratory research,Based on previous literature reports and laboratory research,we plan to hybridizeβ-carboline compounds with pyrido[1,2,3]-triazole compounds,theβ-carboline[1,2,3]-triazoles were synthesized by cyclization at the1,2 and 2,3 positions of theβ-carboline ring,and their biological activities were evaluated.It is hoped that new target compounds with better pharmacological activity can be obtained through the principle of drug splicing.In this thesis,29β-carbolino[1,2,3]-triazole compounds were synthesized by two different methods using L-tryptophan as the starting material;then,usingβ-carbolino[1,2,3]-triazole compound as raw material,react with diaryliodonium salt,screen the reaction conditions,expand the substrate,a total of 61β-carbolino[1,2,3]-triazole salt compounds were synthesized.All the target compounds obtained were characterized by ¹H NMR,¹³C NMR,and HRMS,and the compounds were subjected to in vitro biological activity tests and molecular docking calculations.The cancer inhibitory activity of target compounds against A549（lung cancer cells）,BGC-823（gastric cancer cells）,CT-26（colon cancer cells）,Bel-7402（liver cancer cells）,and MCF-7（breast cancer cells）were evaluated by methyl thiazolyl tetrazolium（MTT）assay,and the structure-activity analysis of the obtained results has laid a foundation for the screening,design and synthesis of new anti-tumor drugs.In addition,we also carried out the molecular docking calculation of the compounds.Through the calculation results,we can know the degree of binding between the target compound and the target protein.On this basis,we can design and synthesize compounds with good drug potential.In conclusion,on the basis of previous laboratory research work,this thesis carried out ring expansion and further structural modification ofβ-carboline compounds to synthesize new compounds with good anti-tumor activity,which will lead to the synthesis of new high efficacy,Low toxicityβ-carboline antitumor drugs have taken another step forward.