New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents

Molecules. 2022 May 23;27(10):3338. doi: 10.3390/molecules27103338.

Abstract

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes' capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

Keywords: Cu+2 complexes; SOD-mimetic and antibacterial activities; crystal structure; cytotoxicity; non-toxic Cu+2 complex; oxidative DNA cleavage; sulfonamides.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antioxidants* / pharmacology
  • Copper / chemistry
  • Ligands
  • Mice
  • Spectroscopy, Fourier Transform Infrared
  • Sulfanilamide
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Thiadiazoles*
  • Xanthines

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Ligands
  • Sulfonamides
  • Thiadiazoles
  • Xanthines
  • Sulfanilamide
  • Copper

Grants and funding

This research received no external funding.