Study On The Structure And Cytotoxicity Of Complexes Based On 5-(Pyrazol-1-yl) Nicotinic Acid

Since cisplatin,carboplatin and similar metal-based drugs have been clinically proven to be effective in treating head cancer,neck cancer,lung cancer and ovarian cancer,chemotherapy has become the main treatment method for most cancers,and sometimes the only option.Although cisplatin and its derivatives have good therapeutic effects,they produce severe normal cytotoxicity,damage normal healthy tissues,cause a variety of adverse reactions,and limit the scope and effectiveness of their treatment.Therefore,the design of new anticancer drugs is imminent.Aroused great interest of drug research and development workers.In the past few decades,the application of lanthanide complexes in the field of biomedicine has increased rapidly.The biological characteristics of lanthanide ions stem from their similarity to calcium ions,low toxicity and other properties.It is this kind of bio-friendliness that makes them satisfactory in the field of biomedicine.The application of lanthanide complexes with multidentate ligands in regulating gene expression and as a promising therapeutic agent has received extensive attention because they have higher biological activity and low toxicity after reacting with organisms.In recent years,people have been interested in the synthesis of lanthanide complexes,DNA interaction and nuclease activity.The earliest metal complex anticancer drugs used clinically are platinum complexes,which affect the apoptosis of cancer cells by affecting the transcription and replication of DNA.Copper（Ⅱ）and zinc（Ⅱ）are endogenous metals in the human body.At the same time,it is also an element necessary for the human body,and the corresponding complexes have been confirmed to have unusual electronic behavior and various chemical reactivity.Copper-zinc complexes can interact with DNA and exhibit good biological redox activity and relatively strong affinity for nucleic acid bases.Certain copper and zinc complexes can generate a large amount of reactive oxygen species（ROS）,which can cause oxidative damage to mitochondria and biological macromolecules,and show strong potential in the field of inorganic anti-tumor.The carboxyl-containing nitrogen heterocyclic ligands have more coordination sites,which can form stable complexes through a variety of coordination methods,and exhibit excellent biological activity.Taking into account the above facts,we chose 5-（Pyrazol-1-yl）nicotinic acid as the ligand and synthesized four novel complexes of Pr（Ⅲ）,Sm（Ⅲ）,Cu（Ⅱ）and Zn（Ⅱ）by hydrothermal method.The crystal structure of the complexes was determined by X-ray single crystal diffractometer,and the elements of the complexes were determined by element analyzer;The ability of complexes 1-4 to bind to fish sperm DNA（FS-DNA）was measured by ultraviolet spectroscopy and fluorescence spectroscopy.The cleavage behavior of agarose gel electrophoresis showed the ability of the four metal complexes to cut p BR322 plasmid DNA.Computer molecular docking simulation experiments show that the two complexes can bind to the target DNA,and form a strong interaction with the base pair of the DNA by inserting;Flow cytometry was used to detect the ability of the complex to induce He La cell apoptosis.And using a fluorescent inverted microscope to observe the apoptosis-inducing effect of metal complexes on human cervical cancer He La cells from the morphological changes;The MTT method was used to study the cytotoxicity of the complex to He La and compared with the clinical drug cisplatin.We explored its binding to DNA at the level of interaction with DNA,and discussed in detail its cytotoxicity to He La cells and apoptosis of cancer cells in in vitro experiments.The IC₅₀values of complex 1 and cisplatin were very similar,while it may become a clinical anticancer drug with high therapeutic effect.