Synthesis, spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

• Published in: Applied organometallic chemistry 2015-06, Vol.29 (6), p.357-367
• Main Authors: Mehta, Jugal V., Gajera, Sanjay B., Patel, Disha D., Patel, Mohan N.
• Format: Article
• Language: English
• Subjects: antimalarial; azodye rhodanine derivative; Bacteria; Binding; Cleavage; Deoxyribonucleic acid; Electronics; Electrophoresis; Herrings; HS DNA; IC50; In vitro testing; LC50; Plasmodium falciparum; Spectra
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.3299

Seven new copper(II) complexes of type [Cu(A)(L)]⋅H2O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (Kb = 1.27–3.13 × 105 M−1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC50 values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC50 values ranging from 5.559 to 11.912 µg ml−1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC50 = 0.62–2.0 µg ml−1). Copyright © 2015 John Wiley & Sons, Ltd. Spectral changes accompanying addition of herring sperm DNA to solutions of complexes indicate intercalative mode of binding of the tetrahedral complexes between DNA base pairs.