Synthesis,Characterization And Biological Activity Aryl (Hetero) Aryl Ring Acylhydrazone And Arene Ruthenium Complexes

Since the second half of the twentieth century, metal anti-cancer drugs have developed rapidly. The study of construction and synthesis of the metals anti-cancer drugs has been a hot topic. Half-sandwich arene ruthenium complexes possess unique molecular structure, which can interact with DNA molecules in a variety of ways, and we can obtain antitumor complexes with different antitumor activities by changing the ligand. Hydrazone compounds itself has a certain biological activity, and molecule contain carbonyl oxygen, imine nitrogen and other donor atoms, which can coordinate with many kinds of metals to improve its biological activity. Therefore, this paper selects the hydrazone compounds as ligands to construct new arene ruthenium complexes.This paper took benzoyl hydrazine, isoniazid and aromatic (hybrid) ring aldehyde as raw materials, and synthesised nine hydrazone ligands L1～9, which are benzaldehyde benzoyl hydrazone (L1),4-methoxybenzaldehyde benzoyl hydrazone (L2),4-nitrobenzaldehyde benzoyl hydrazone (L3), furan-2-carboxaldehyde benzoyl hydrazone (L4),1-naphthaldehyde benzoyl hydrazone (Ls), benzaldehyde isonicotinoyl hydrazone (L6),4-methoxybenzaldehyde isonicotinoyl hydrazone (L7), furan-2-carboxaldehyde isonicotinoyl hydrazone (Ls), and 1-naphthaldehyde isonicotinoyl hydrazone (L9). The structure of the ligands were characterized by IR and 1HNMR.Based on the above hydrazone compounds as ligand, nine novel arene ruthenium complexes [(η 6-p-cymene)RuL1～9Cl][Cl] were synthesized after reacting with precursor [(η6-p-cymene)RuCl2]2, whose structures were confirmed by IR, UV absorption spectrum and 1HNMR. The results showed that the neutral ligand coordinated with the precursor [(η 6-p-cymene)RuCl2]2 by carbonyl oxygen atom and nitrogen atom in the molecule, generating hydrazone arene ruthenium complexes with pseudo eight plane structure.The interaction mode between complex [(η6-p-cymene)RuL1～9Cl][Cl] and calf thymus DNA was studied by UV spectrometry and viscometric studies, the results showed that the combination methods between 9 complexes and DNA were intercalative mode. The combination strength between complex [(η6-p-cymene)RuL1Cl][Cl] and calf thymus DNA was the strongest, and it between complex [(η6-p-cymene)RuL2Cl][Cl] and calf thymus DNA was the weakest. Overall, The combination strength between DNA and benzoyl hydrazone arene ruthenium complexes was stronger than that between DNA and isoniazone arene ruthenium complexes. The in vitro anticancer activity of arene ruthenium complexes against human lung cancer cell A495 with IC50 values in the range of 17.96～46.25 μM.