Study On Synthesis And Anti-tumor Activities Of Paeonol Derivatives

To prevent and cure serious diseases such as cancer, infectious disease, cardiovascular disease, trauma and digestive diseases and to improve human health has been the main goal pursued by the medical profession. Tumor occurrence and development were not only related to abnormal differentiation and proliferation of cancer cells but also to apoptosis decrease. Thus to research and develop the new drugs of inducing apoptosis of tumor cells would be a new way for curing cancer. Recent reports indicated paeonol have anti-tumor activities both in vivo and in vitro and induce tumor cell apoptosis. The expression of apoptosis-related genes may be one of the mechanisms.In this paper, paeonol was synthesized by two-step of acetylation, methylation of resorcinol. Then paeonol as a precursor condensation of the ketone carbonyl of paeonol weith various amine compounds, to synthesize a series of Schiff base derivatives of paeonol, and Schiff base derivatives as ligand to synthesize metal complexes. The Anti-tumor activities of the target compounds were determined by MTT assay.The main work of this paper:1. Synthesis of paeonol by phase-transfer Catalysis: paeonol was synthesized from resorcin through two steps of acetylating and methylate with methyl iodide, using TBAB as the phase transfer catalyst, moreover paeonol was purified by steam distillation. The total yield was 68.32%, the structure of paeonol was confirmed by UV, IR. The method was simple, stabilize and could be applied in the industrial production.2. Synthesis of paeonol derivatives: Schiff base derivatives: N'-[1-(2,4-dihydroxyphenyl)ethylid-ene]benzohydrazide (B1) Bi(2',4'-dihydroxy-α- methylbenzylidene)-diimine (B2) Bi(2',4'-dihydroxy-α-methylbenzyl-idene)-ethylenediimine (B3) Bi(2',4'-dihydroxy-α-methylbenzyl-idene)-1,3-trimethylenediimine (B4) 5-methoxy-2-[-1-(propylimino)ethyl]phenol(P1) Bi(2'-hydroxy-4'-methoxy-α-methyl-benzylidene)-diimine (P2) Bi(2'-hydroxy-4'-methoxy-α-methyl-benzylidene)-ethylenediimine(P3) Bi(2'-hydroxy-4'-methoxy-α-methyl-benzylidene)-1,3-trimethylenediim-ine(P4) Metal complexes: CuB1,CuPae,RuP3,RuP4, and CuB1,RuP3,RuP4 three compounds have not been reported.3. The anti-tumor activities of eight of the paeonol derivatives were determined by MTT assay. The results showed that paeonol derivatives suppress proliferation of K562,HL60 cells in a dose-dependent manner. The inhibiting rate of CuB1 on K562 cells was the highest with IC50 6.94μg/mL, then IC50 of CuPae, RuP4, RuP3 were 8.58μg/mL ,10.65μg/mL,17.72μg/mL respectively. The inhibiting rate of CuPae on HL60 cells was the highest with IC50 1.96μg/mL, then IC50 of CuB1, RuP4, RuP3 were 2.03μg/mL, 9.31μg/mL, 9.55μg/mL respectively. Which showed CuB1 and CuPae display higher inhibitory activities on proliferation of K562,HL60 cells in a dose-dependent manner, they could be used as research emphasis to further development of this kind compounds.