Synthesis,Bioactivity And Electrochemistry Analysis Of Ferrocene Derivatives

This article using the Discovery Studio 3.1 system, the selection of enzyme aromatase (AR, CYP19) (breast cancer) and mutated EGFR kinase domain (L858R), EGFR kinase domain T790M mutation (non-small cell lung cancer) as a receptor for computer simulation of ferrocene heterocyclic derivatives and molecular docking, preliminary results have showed that ferrocene heterocyclic derivatives and binds to a receptor protein ability better than ferrocene itself.In this paper by ferrocene carboxylic acid, and 7 kinds of nitrogen heterocyclic compound as a raw material,18 species of ferrocene was synthesized heterocyclic derivatives; And in the reaction to choose EDC1, HOBt or DMAP as condensing agent, dichloromethane as solvent system,24 hours at room temperature under the condition of reaction synthesis effect is best; All the target compounds structure by IR, MS,1H NMR,13 C NMR and HR MS characterization; At the same time, through the 3-(4,5-dimethyl-2 away between the seconds)-2,5-diphenyl four azole nitrogen bromine salt (determined by MTT) method, a preliminary test of the new compound activity against breast cancer and non-small cell lung cancer, the experiment with ferrocene as the positive control in the process.Compound Fcl, Fc4-5, Fc8-9, Fcll-12, Fc14 and Fc16-17 through determined by MTT method to test the inhibition activity of breast cancer (MCF-7 cell). Results showed that compound Fc3,Fc11,Fc12 and Fc17 showed some inhibitory activity, its IC50 alue concentration were 39.2,44.2,48.3, and 24.2 μmol·L-1. In the eight tested its inhibition of breast cancer (MCF-7 cell) activity of compounds, the results showed:containing pyridine ring and into ester ferrocene heterocyclic compound, its inhibition of the activity of breast cancer than those who do not containing pyridine ring and into amide ferrocene heterocyclic compounds. In molecular simulations, the compound Fcl-Fc18 as ligand and aromatase receptor (AR, CYP19) docking site, hope to be able to explain why the compound Fc17 had the best inhibiting the activity of breast cancer (MCF-7 cell). We observed in the docking compounds are best spent Fc17 and the receptor, its docking with the receptor to form the two hydrogen bonds, Thr310 with amino acid residues and Ser314 respectively.Compound Fcl, Fc4-5, Fc8-9, Fc11-12, Fc14 and Fc16-17 through determined by MTT method to test the inhibition activity of non-small cell lung cancer (H1299 cells). The results showed that compound Fc14 showed some inhibitory activity, its IC50 value concentration of 78.3 μmol·L-1; And for the same instead of heterocyclic compounds, the longer the Linkage of C chain and the stronger the effect of the inhibition of H1299 cells. In molecular simulations, the compound Fcl-Fc18 as ligands to the epidermal growth factor receptor docking site, hope to be able to explain why the compound Fcl4 had the best inhibiting the activity of non-small cell lung cancer (H1299 cells). We observed in the docking compounds are best spent Fc14 and the receptor, its docking with the receptor to form a PI-PI bond, and van der Waals force and amino acid residues 2eb3 forms a hydrogen bond. Using cyclic voltammetry study ferrocene REDOX properties of nitrogen heterocyclic derivatives, results show that:the connection of the induced effect of carbonyl and compounds in key itself effect common conjugate compounds.