Synthesis And Antitumor Activity Of Platinum(Ⅱ) Complexes With Schiff Base And Its Derivatives As Ligands

Platinum(Ⅱ) complexes with a square-planar structure could form covalent compoundswith cellular DNA and make the DNA strands single-stranded or double-stranded break ordistorted, thus leading to the cancer cell death. It can be used as antitumor drugs.Chapter1: The current progresses of metal complexes antitumor drugs were reviewedhere, particularly the development and classification of platinum drugs.Chapter2:11amino acid Schiff bases platinum(Ⅱ) complexes were synthesized. All theligands and complexes were characterized by EA, IR and1H NMR. The results showed thatthe metal ion was coordinated with phenolic hydroxyl O, amino acid carboxyl O and imine Natoms. The in vitro antitumor activity against human lung cancer cell line A549and humanuterus cancer cell line Hela was determined with MTT assay, and part of the compounds weretested for their DNA interaction ability with the salmon sperm DNA using ultravioletspectrum. The results showed that the cytotoxic activity of complexes with L-amino acidSchiff bases as ligands was of selectivity. Hyperchromicity occurred after coordinationbetween complexes and salmon sperm DNA, the binding mode was might for intercalation.Comparing with cisplain, K[Pt(3-hydroxy-2-(2,5-dihydroxybenzylideneamino)propionyloxy)Cl](4f), K[Pt(2-(5-bromo-2-hydroxybenzylideneamino)-4-methylpentanyloxy)Cl](4j) andK[Pt(2-(5-bromo-2-hydroxy benzylideneamino)-3-hydroxybutanyloxy)Cl](4k) exhibitedbetter cytotoxic activities against Hela cell line, K[Pt(3-hydroxy-2-(2-hydroxybenzylideneamino)butanyloxy)Cl](4e) displayed similar cytotoxic effect against Hela cell line.Chapter3:8reduced amino acid Schiff bases platinum(Ⅱ) complexes were synthesized.All the ligands and complexes were characterized by EA, IR, MS and1H NMR. The resultsshowed that the metal ion was coordinated with phenolic hydroxyl O, amino acid carboxyl Oand amino N atoms. The in vitro antitumor activities of the platinum compounds have beenvalidated against the human acute promyelocytic leukemia cell line HL-60, humannasopharyngeal carcinoma cell line KB, human gastric carcinoma cell line BGC-823and thehuman liver carcinoma cell line Bel-7402by MTT assay, and part of compounds were testedfor their DNA interaction ability with the salmon sperm DNA using ultraviolet spectrum. The results showed that the reduced amino acid Schiff bases complexes have selectivity againsttested carcinoma cell lines. Hyperchromicity occurred after coordination between complexesand salmon sperm DNA and the binding mode was might for intercalation. The cytotoxicityof complex K[Pt(2-(5-bromo-2-hydroxybenzylamino)-4-methylpentanyloxy)Cl](6j) is betterthan that of cisplatin against BGC-823and HL-60cell lines, and show close cytotoxic effectagainst Bel-7402cell line.Chapter4:5sterically hindered platinum(Ⅱ) complexes were synthesized and differentialpulse voltammetry was employed to monitor the interaction between ssDNA and complexes.The results showed that [Pt(N,N’-bisalicylidene-1,2-ethylenediamine)] had the best interactionwith DNA, substituents on ligands can effectively influence the interaction between Ptcomplexes and DNA, bulky substituents on ligands can effectually embarrass the coordinationof Pt(Ⅱ) ion to guanine and adenine residues.