DNA binding properties and cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)ben- zohydrazone and (E)-N'-((thiophen-2-yl)methylene) isonicotinylhydrazone

OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) bind-ing properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thio-phen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhy-drazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)ison-icotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal com-plexes were investigated by UV-Vis spectropho-tometry and viscosity titration. The toxicologi-cal properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tri-dentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)(2)], [Ni(HL1)(2)], [Cu(HL1)(2)], [Co(L-2)(2)], [Cu(L-2)(2)], [Zn(L-2)(2)], [ScL2(NO3)(2)(H2O)(2)], [Pr(L-2)(2)(-NO3)] and [Dy(L-2)(2)(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 10(4)similar to 10(5) L mol(-1) compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 x 104 L mol(-1)]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)(2)] and [Cu(HL1)(2)] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 mu mol L-1 and 2.2 mu mol L-1, respectively. CONCLUSIONS: These compounds, espe-cially [Ni(HL1)(2)] and [Cu(HL1)(2)], will be promis-ing for anti-tumor drugs, which should be fur-ther studied.

Automated summary

This study aimed to investigate the CT-DNA binding properties and HeLa cell viabilities of metal complexes derived from H2L1 and HL2. A series of metal complexes derived from H2L1 and HL2 were synthesized, and their structures were characterized. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation, and the groove pattern cannot be excluded. The presence of [Ni(HL1)(2)] and [Cu(HL1)(2)] showed lower viabilities in HeLa cells, indicating their potential as anti-tumor drugs.