Design, synthesis, in vitro anticancer, antioxidant and antibacterial activity; DNA/BSA binding, photoleavage and docking studies of Cu(II) ternary metal complexes

Abstract

Three mononuclear, mixed ligand ternary Cu(II) complexes of 3-((Z)-1-(2-hydroxyphenylimino)ethyl)-4-hydroxy-6-methyl-2H-pyran-2-one (HEHMP) viz; [Cu-(Phen) (HEHMP)] (1a), [Cu-(Bpy)(HEHMP)] (1 b) and [Cu-Bpy(NCS)(HEHMP)] (1c) were synthesized and characterized by data obtained from various spectral techniques. The binding affinities of these complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein were explored by absorption and fluorescence quenching titrations. The results indicated strong affinity of the title compounds to bind with both CT-DNA and BSA. The antioxidant properties of the synthesized compounds evaluated by free-radical scavenging method using spectrophotometric technique indicated their affirmative potential activity. Gel electrophoresis experiments revealed the efficacy of metal complexes in resulting the cleavage of pBR322 supercoiled DNA. In vitro cytotoxicity studies of these complexes evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HeLa and MCF-7 cancer cell lines indicated relatively high effectiveness of the complex 1c. Confocal microscopy signified the potential of the complexes to induce apoptosis in HeLa cell lines. In addition, the antibacterial activity of the compounds carried out by disc diffusion method revealed significantly enhanced antibacterial activity in Cu (II) ternary complexes compared to the activity of ligands in unbound form signifying the implicit role of metal ion in inducing lipophilic character.

Keywords:

• DNA/BSA Binding
• Cytotoxicity
• Antimicrobial activity
• Antioxidant
• Docking Studies

Acknowledgements

We are grateful to the University Grant Commission (UGC) New Delhi, India for providing the RGNF-ST-AND-9591 Fellowship as financial assistance to one of the authors and DST-PURSE-II. The authors are thankful to the Department of Chemistry and Department of Biochemistry Osmania University, Hyderabad for providing the research facilities. We also grateful to the National Institute of Nutrition (NIN) and Center for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad for providing facilities in carrying out cytotoxicity studies. We are deeply thankful for the generous funding extended from UGC-FAR and DST-PURSE Projects-II.

Supplementary information

Supporting Information: Additional information pertaining to ¹H, 13C-NMR, SEM-EDX, Mass, FT-IR spectra, TGA-DTA and UV-Vis of title compound and its complexes (Figures S1–S14) are given in the supporting information.