| Objective:Salicylic aldehyde in medicine, environmental engineering, chemical dyes all showed good activity. Meanwhile with active carbonyl carbon, it is one of the important organic synthesis intermediates. Many studies have shown that salicylic aldehyde schiff’s base has certain biological activity. 4-Aminosalicylic acid is the second-line drug resistant TB, and have anti-inflammatory, reducing blood fat, the effect of treatment of ulcerative colitis roles, containing phenol hydroxyl, carboxyl, amino three very active functional groups. So this paper takes salicylaldehyde derivative and 4-aminosalicylic acid as the raw materials to form four kinds of schiff base, and choose 5-methyl-salicylaldehyde-4-aminosalicylic acid schiff base which is better than others in antitumor as ligand to form complexes with metal ions. Antitumor activity in vitro experiments determined by MTT assay, and bacteriostatic ring experiment were carried out to study the bacteriostatic action, series complexes and the interaction mechanism of bovine serum albumin(BSA)were studied. The work research on antibacterial, antitumor drug is of great significance.Methods:1. Salicylidene-4-Aminosalicylic acid Schiff base complexes was obtained from 4-aminosalicylic acid and 5-substituted salicyldehyde derivatives(F, Cl, Br, CH3)in ethanol solution. Treament of the ligand 5-methyl-salicylaldehyde-4-aminosalicylic acid Schiff with the metal salt gave the corresponding complexes respectively{M=Cu, Ni, Co, La, Pr, Ce, Er, Gd, Dy}. Its structure and composition was determined through elemental analysis, MS, UV, IR, 1HNMR.2. Anti-tumor activity in vitro experiments were carried ouy by MTT methoed. Use it to test four kinds of schiff base antitumor activity. The antitumor activity of nine kinds of complexes and their ligand in three concentration gradient(0.5 μM, 1.0 μM, 2.0 μM), were examine on human cervical carcinoma cell Si Ha(HPV-16 positive cervical carcinoma cell line), and He La(HPV-18 positive cervical carcinoma cell line), to screene out good activity complexes. On this basis, the concentration gradient to achieve the supprering rate were expanded to five concentrations(0.5 μM, 1.0 μM, 1.5 μM, 2.0 μM, 2.5 μM). Meanwhile by plotting the concentration-dose-response curves, half inhibitory concentration(IC50) were gotten. Then A0/EB double staining methods, observe the effect of drugs on cancer morphology. 3. Inhibition zone method was tested on the ligand and complexes by Escherichia coli, Staphylococcus aureus. The inhibition rate was determined the minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC). 4. The interaction between Schiff base and bovine serum albumin(BSA)was studied by fluorescence spectra. By concentration of BSA, with increasing the concentration series complexes, scanning fluorescence spectroscopy and synchronous fluorescence. The binding sites and thermodynamic parameters were calculated. Spectra were got site binding model and the formula for solving the thermodynamic binding constants at different temperatures.Results:1. Synthesis of Salicylic-acetal Schiff base complexes, HL-F, the molecular formula is C14H10NO4F; HL-Cl, the molecular formula is C14H10NO4Cl; HL-Br, the molecular formula is C14H10NO4Br; HL-CH3, the molecular formula is C15H13NO4. Then the HL-CH3 form complexes with nine metal ions, and the complexes were analyzed by elemental analysis, IR, UV and etc. It is showed that the central metal ion were combined with imino nitrogen atom, an oxygen atom of the phenolic hydroxyl group and two molecules of water to form a six-membered ring chelate, the coordination number of the central metal ion is 6, and molecular formula is [C30H24N2O8Na2M ]?2H2O. 2. MTT assay showed that four kinds of schiff base has showed strong activity on two tumor cells, with the inhibition rates HL-F<HL-Cl<HL-Br<HL-CH3, predicting that the anticancer activity is correlated with salicylaldehyde substituent electronic effects associated. Series complexes on the activity of Si Ha superior to He La, after the formation of the complex to enhance the anti-tumor activity. The copper complexes has the best anti-tumor activity, get ligands and copper complexes IC50 value concentration of Si Ha effect after 24 h were 2.50 μmol/L, 0.80 μmol/L, He La is 3.29 μmol/L, 0.90 μmol/L, through mapping concentration concentration-response curves. A0/EB method observed copper complexes can not only accelerate the apoptosis of cancer cells but also kill cancer cells. 3. Bacteriostatic ring test showed that series complexes has inhibition on escherichia coli, and staphylococcus aureus, especially for staphylococcus aureus. Lanthanum complexes bacteriostatic activity is better than other complexes, as determined by MIC(6.25 μg/m L,3.13 μg/m L) and MBC(50 μg/m L,25 μg/m L). 4. It was static quenching effect between complexes and BSA. Through thermodynamics derived ligands with BSA types of the binding force is Van Der Waals and Hydrogen bonding forces, its complexes is same with the ligand. Meanwhile the number of binding sites is 1. Synchronous fluorescence spectrum showed that the ligand has no impact on the conformation of BSA.Conclusions:In this paper, four Salicylic aldehyde Schiff base compands were synthesis. HL-CH3 exhibit good antitumor activity. Then HL-CH3 complexed with nine metal to form complexes. Series complexes have showed good antibacterial and antitumor activity, and the complexes is better than ligands. Types of the binding force with BSA is Van Der Waals and Hydrogen bonding forces. The above work has important reference and guidance for further study of bioactive amino salicylic acid Schiff bases. |
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