A novel Schiff base derived from the gabapentin drug and copper (II) complex: Synthesis, characterization, interaction with DNA/protein and cytotoxic activity

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2016-09, Vol.162, p.34-44
• Main Authors: Shokohi-pour, Zahra, Chiniforoshan, Hossein, Momtazi-borojeni, Amir Abbas, Notash, Behrouz
• Format: Article
• Language: English
• Subjects: Amines - chemistry; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Copper (II) complex; Copper - chemistry; Crystallography, X-Ray; Cyclohexanecarboxylic Acids - chemistry; Cytotoxic activity; DNA - chemistry; Drug Screening Assays, Antitumor; Gabapentin; gamma-Aminobutyric Acid - chemistry; Humans; Interaction with DNA and BSA; Ligands; Mass Spectrometry; Proteins - chemistry; Schiff base; Schiff Bases - chemistry; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2016.06.022

A novel Schiff base [C20H23NO3], has been prepared and characterized using FT-IR, UV–vis, 1H NMR spectroscopy, elemental analysis and X-ray crystallography. A copper (II) complex [Cu(C20H22NO3)2]·H2O has also been synthesized and characterized. The new ligand and complex thus obtained were investigated by their interaction with calf thymus DNA and BSA using electronic absorption spectroscopy, fluorescence spectroscopy, and thermal denaturation. The intrinsic binding constants Kb of the ligand and Cu (II) complex, with CT-DNA obtained from UV–vis absorption studies were 1.53×104M−1 and 3.71×105M−1, respectively. Moreover the addition of the two compounds to CT-DNA (1:2) led to an increase of the melting temperature of DNA up to around 2.61°C for the ligand and 3.99°C for the Cu (II) complex. The ligand and Cu (II) complex bind to CT-DNA via a partial intercalative, as shown by the experimental data. In addition, the albumin interactions of the two compounds were studied by fluorescence quenching spectra, the results indicating that the binding mechanism is a static quenching process. The in vitro cytotoxicity of the two compounds on three different cancer cell lines was evaluated by MTT assay. The results showed that the copper complex exerted enhanced cytotoxicity compared with the Schiff base ligand; thereby, this complex clearly implies a positive synergistic effect. Furthermore, the copper complex showed a high, selective, and dose-dependent cytotoxicity against cancer cell lines. DNA & BSA interaction with novel Schiff base. [Display omitted] •Synthesis and characterization of a novel Schiff base derived from the gabapentin drug and copper (II) complex•The ligand and copper (II) complex partial intercalative into the base pairs of DNA•The two compounds indicate good binding propensity to BSA.•The two compounds have excellent anticancer activity against JURKAT, SKOV3 and U87 cell lines.