Ruthenium complexes with mono- or bis-heterocyclic chelates: DNA/BSA binding, antioxidant and anticancer studies

J Biomol Struct Dyn. 2021 Jul;39(11):4077-4088. doi: 10.1080/07391102.2020.1775126. Epub 2020 Jun 11.

Abstract

Deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) binding interactions for a series of ruthenium heterocyclic complexes were monitored using ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence emission spectroscopy and agarose gel electrophoresis. Investigations of the DNA interactions for the metal complexes revealed that they are groove-binders with intrinsic binding constants in the order of 104 - 107 M-1. Electronic spectrophotometric DNA titrations of the bis-heterocyclic metal complexes illustrated hypochromism of their intraligand electronic transitions and the presence of diffuse isosbestic points which are synonymous with homogeneous binding modes. Metal complexes with the mono-heterocyclic chelates also showed alterations in their intraligand transitions and changes in their metal-based electronic transitions which are suggestive of metal coordination to the CT-DNA structure. Using agarose gel electrophoresis assessments, Hoechst DNA binding competition studies corroborate that the metal complexes are DNA groove-binders. Optimal uptake of these metal complexes by BSA was observed based on their optimal apparent association and Stern-Volmer constants (Kapp and KSV > 104 M-1). Radical scavenging studies revealed that the metal complexes have high activities towards the neutralization of NO and DPPH radicals. Data attained from the BSA electronic spectrophotometric titrations for the majority of the metal complexes illustrated distinct hyperchromism accompanied with blue shifts which indicates unwinding of the protein strands. Predominately, the metal complexes showed moderate cytotoxicity against both triple-negative breast cancer and cervical cancer cell lines that was greater than that of 5-fluorouracil.Communicated by Ramaswamy H. Sarma.

Keywords: DNA/BSA binding; Ruthenium heterocyclic complexes; antioxidant activities; cytotoxicity.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antioxidants / pharmacology
  • Coordination Complexes* / pharmacology
  • DNA / metabolism
  • Humans
  • Protein Binding
  • Ruthenium*
  • Serum Albumin, Bovine / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Coordination Complexes
  • Serum Albumin, Bovine
  • Ruthenium
  • DNA