Thesis (Ph.D.)--Chulalongkorn University, 2011

The Fe(III), Co(II), Ni(II), and Cu(II) complexes with 6-deoxyclitoriacetal (L) have been synthesized. The proposed molecular structures based on spectroscopic methods, EA, and TGA are as follow: FeL(H2O)4Cl2 (1), CoL(NO3)(H2O)2 2H2O (2), NiL(CH3COO) 4H2O (3), and CuL2 2H2O (4). All complexes are non-cytotoxic to normal cell lines of human liver cell (CH), skin fibroblast (CCD), and foreskin fibroblast (HS27). L showed strong cytotoxicity against BT474 (IC50 0.003 µM), good activity against CHAGO, KATO, HepG2, SW620 (IC50 0.136-0.216 µM), and moderate against KB, NCI-H187, and MCF7 (IC50 0.654-0.764 µM). Complexes 1, 2 and 3 exhibited strong cytotoxicity to cell lines of KB, CHAGO, and KATO3 with IC50 in the range of 0.002 µM to 0.007 µM. Only 4 has strong cytotoxicity for all tested cell lines except KB. All complexes and free ligand can bind with CT-DNA by intercalation mode observed with UV-Vis, fluorescent, and Tm. techniques. Another part of this project is to synthesis and cytotoxic evaluation of Ni(II), Cu(II) and Zn(II) with two Schiff base ligands: 2-[(4-chlorobenzylimino)-methyl]-phenol (A) and 2-[(4-methoxybenzylimino)-methyl]-phenol (B). The X-ray crystal structures of complexes NiA2 (A1), CuA2 (A2), NiB2 (B1), and CuB2 (B2) are square planar, while ZnA2 and ZnB2 complexes (complexes A3 and B3) showed tetrahedral geometry. All complexes are non-cytotoxic to normal kidney cell line of an African green monkey (vero cell). The potent cytotoxic activities have shown for Cu(II) and Zn(II) complexes against all tested cancer cell lines, especially Cu(II) complexes (B2) against KATO3 (IC50 25 nM) and BT474 (IC50 1.45 nM). DNA binding studies revealed the strong binding constant (Kb) of Cu(II) and Zn(II) complexes. By UV-Vis, fluorescent and Tm, the binding mode of Cu(II) and Zn(II) complexes were confirmed to be intercalation. However, Ni(II) complexes were found to bind with CT-DNA by groove binding mode and it is inactive to all tested cancer cells.