DNA-binding And Antitumor Properties Of New Dissymmetrical N, N'-disubstituent Oxamide Compounds

Studies on DNA interaction of organic and inorganic small molecules have gotten more and more interests in the recent years. Deoxyribonucleic acid (DNA) is an important genetic substance in organism. As the basis of genetic expression, it plays an important role in the process of storing, copying and transmitting germ messages. The recognition of DNA for natural and artificial molecules in the inhibition of cellular disorders and in therapy of certain diseases is very paramount importance in inorganic biochemistry. The binding of small molecules, especially transition metal complexes, to DNA and molecular identification are very important in life science. It can provide useful information to design novel and efficient drugs for disease diagnosis and chemotherapeutic agents. The main purpose of this article is to study the structure-activity relationship of the oxamide compounds and DNA. The DNA-binding properties of these oxamide compounds have been examined using electronic absorption, fluorescence, viscometry and electrochemical technique, and their antitumor activities have also been studied in vitro by SRB assay.1. Four novel dissymmetrical N,N'-bis(substituent)oxamide ligand, N-phenolato- N'-(3-dimethylaminopropyl)oxamide (H3pdmapo) (L1), N-phenolato-N'-(2-dimethyl- aminoethyl)oxamide (H3pdmaeo) (L2), N-phenolato-N'-(3-aminopropyl)oxamide (H3papo) (L3) and N-2-(dimethylamino)ethyl-N'-3-(dimethylamino)propyl oxamide (H2dmaepoxd) (L4) have been synthesized and characterized by MS, 1H NMR, IR and elemental analyses.2. Sixteen complexes with these dissymmetrical N,N'-bis(substituent)oxamides as ligands, [Cu₂(pdmapo)(phen)(H₂O)](ClO4) (1), [Cu₂(pdmapo)(bpy)(CH₃OH)](ClO₄) (2), [Cu₂(pdmapo)(dabt)](CH₃OH)(ClO₄) (3), [Cu₂(pdmaeo)(phen)(H₂O)](CH₃OH)- (ClO₄) (4), [Cu₂(pdmaeo)(dabt)](CH₃OH)(ClO₄) (5), [Cu₂(papo)(bpy)(H₂O)](ClO₄) (6), [Cu₂(papo)(dmbpy)(CH₃OH)₀.5(H₂O)0.5](H₂O)0.5(ClO₄) (7), [Cu₂(dmapoxd)- (phen)₂](ClO₄)₂ (8), [Cu₂(dmapoxd)(bpy)₂](ClO₄)₂ (9), [Ni₂(dmapoxd)(bpy)₂(H₂O)₂]- (ClO₄)₂ (10), [Cu₂(dmaepoxd)(N₃)₂]_n (11), [Cu₂(dmaepoxd)(CH₃CH₂OH)(SCN)₂]₂n (12), [Cu₂(dmaepoxd)(CH3OH)(SCN)2]2n (13), [Cu₂(dmaepoxd)(NO2)2]n (14), [Cu₂(dmaepoxd)(pic)₂]n?nCH₃OH (15) and [Cu₂(dmaepoxd)(pma)]n (16), have been synthesized and characterized by X-ray single crystal diffraction. The coordination environments of the metal atoms in the complexes are explored. Hydrogen bonds andÏ€-Ï€stacking interactions which stabilize the crystal structure in these complexes are also discussed.3. The DNA-binding properties of the compounds have been studied by electronic absorption, fluorescence, viscometry and electrochemical technique. The results suggest that the ligands L1^L4 and complexes (11)¹⁴ bind to DNA via a groove binding mode while complexes (1)¹⁰ and (15)¹⁶ bind intercalatively to DNA. The structure-activity relationship of these oxamide compounds binding to DNA has been examined.4. The cytotoxicities of ligands L1^L4 and its complexes (1)¹⁶ are examined in vitro by SRB assay. The results indicate that some compounds showed different cytotoxic activities against SMMC-7721 and A549 cell lines. Among these compounds, complex (8) has the strongest effects, with IC50 values 20 and 16 ng/mL in the two human tumor cell lines, respectively.The researches of the paper not only enriched the content of inorganic medicinal chemistry, but also supplied valuable information for design and synthesis of inorganic antitumor medicinal with high activity and low toxicity.