Synthesis, Characterization And Biological Activity Of 2-Hydroxy-4-Methoxybenzaldehyde Schiff Bases

The synthesis, characterization, antioxidant and antitumor activity of 10 types of 2-hydroxy-4-methoxybenzaldehyde Schiff base derivatives were studied in this paper, and 9 compounds were firstly synthesized, which were characterized by IR, UV, 1H NMR and elemental analysis, and the crystal structures of 8 compounds were determined by X-ray single crystal diffraction analysis.1.10 types of 2-hydroxy-4-methoxybenzaldehyde Schiff bases were synthesized, such as 5-methoxy-2-[(E)-(pyridin-2-ylimino)methyl]phenol(a),5-methoxy-2-[(3-methylpyridine-2-yl mino)methyl]phenol(b),5-methoxy-2-[(4-methylpyridine-2-ylimino)methyl]phenol(c),5-nethoxy-2-[(4-methylpyridine-2-ylimino)methyl]phenol(d),5-methoxy-2-[(E)-(pyridin-3-yl mino)methyl]phenol(e),5-methoxy-2-[(E)-(pyrimidin-2-ylimino)methyl]phenol(f),5-methoxy-2-[(benzimidazol-2-ylimino)methyl]phenol(g),5-methoxy-2-[(thiazol-2-ylimino)methyl]phenol (h),5-methoxy-2-[(E)-(benzothiazol-2-ylimino)methyl]phenol(i),4-{[(E)-(2-hydroxy-4-methoxyphenyl)methylidene]amino}benzenesulfonamide(j).9 compounds were firstly reported except the compound i.2. The synthetic conditions of compounds d and j were researched. The maximum yield 72.06% of compound d was obtained by the reaction of 1.7:1 molar ratio of 2-hydroxy-4-methoxybenzaldehyde with 2-amino-6-methylpyridine under the temperature of 75 ℃ for 5 h. The optimum conditions of compound j were as follows:2.5:1 molar ratio of 2-hydroxy-4-methoxybenzaldehyde and 4-amino-benzenesulfonamide reacted at 75℃ for 2.5 h. The yield of compound j was up to 87.42%.3. The crystal structures of 8 compounds were characterized by single X-ray crystal diffraction method. Compounds a and b belong to monoclinic system with space group P2i and P21/n, respectively. Compounds c and e belong to orthorhombic system with space group P212121. Compounds d, h and i belong to monoclinic system with space group P21/c. Compound j belongs to orthorhombic system with space group Pbca.4. The in vitro antioxidant activity of the object compounds were tested by DPPH (1,1-diphenyl-2-picryl-hydrazyl) method. The results showed that the object compounds had scavenging activity on DPPH free radical. Compounds d, e and f showed relative good scavenging activity, which ICso (50% inhibitory concentration) was 0.294,0.502 and 0.617 mg/L, respectively. The scavenging effects of the object compounds on DPPH free radical were linear with their concentration in the range of 5-200 mg/L.5. The in vitro antitumor activity of the object compounds and their Zn(Ⅱ) coordination compounds against SMMC-7721, MCF-7, HepG2 and SGC tumor cells were tested by high throughput screening (HTS) assay. The results showed that all the compounds had weak inhibition effect on the growth of the tumor cells at the concentration of 10 μmol/L. The inhibition of the compound a～j and their Zn (Ⅱ) coordination compounds against the tumor cells had no apparent difference.