Study On A Novel Sythetic Compound Of Neuro-protective Effect And Its Mechanism

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, with the number of patients will gradually over cancer will become the world’s second leading cause of death in the disease. Alzheimer’s disease, also as senile dementia, China is the largest country in the world on the base of an aging population, the number of people were suffering from the Alzheimer’s disease and growth rate was ranked first in the world, due to the high incidence of Alzheimer’s disease and low treatment reason, so that in the development of Alzheimer’s drugs caused a worldwide concern; Parkinson’s disease, also as the world’s second-largest of the central nervous degenerative disease has seriously disturbed the quality of life of many patients everyday, it has not yet been developed to eradicate the drug, so the development of prevention and treatment of Parkinson’s disease drugs will become a very urgent problem in the future.Pyridine derivatives as an important class of heterocyclic compounds, was a widely present in natural products, active drugs, applications in pharmaceutical, chemical pesticides, and other fields; as the nature of a class of small molecule compounds naphthoquinone was having a variety of biological activity, plays a vital role in medicine, pesticides, dyes and other production aspects, because of their special chemical properties, but also as a preservative and disinfectant. The thesis of pyridine derivatives and naphthoquinone compounds was a new synthesis, in which the synthesis of novel dihydropyridine compound in a yield of up to 77% named 5zou; synthesis of novel naphthoquinone compound yield 95% named 3h8 b.A large number of experiment shows that as a neurotoxin glutamat e or 6-OHDA were parts of the pathogenesis of Alzheimer’s disease and Parkinson’s disease, so this paper administration 25 m M L- glutamate on damage treatment of Alzheimer’s disease model and take 100μM 6-OHDA-induced for the Parkinson’s disease model; after successful modeling, using the percentage of apoptotic cells detected by MTT; and the number of apoptotic cells was observed phenomenon of Hochest 33342; Fluo-4-AM fluorescence staining of calcium content; JC-1 fluorescence probe analyzes changes in mitochondrial membrane potential; accumulation DCFH-DA staining to detect reactive oxygen species; Western blot method to detect apoptosis related protein Bcl-2, Bcl-x L expression.It has been proved, and the synthesis of novel compounds 5zou or 3h8 b can significantly reduce the cell apoptosis, inhibit the increase of the L- glutamic acid and 6-OHDA-induced calcium ion concentration in intracellular, reducing the mitochondrial membrane potential reduction, mitigation within the modeling of drug was induced the PC12 cells intracellular ROS excessive accumulation and increase Bcl-2-expressing cells, Bcl-x L, and thus prove the thesis novel compounds synthesized on 6-OHDA and L-glutamate-induced PC12 cells have a significant protective effect, it can be used as the first choice for the treatment or prevention of degenerative diseases of the central nervous drugs.