Title
Novel mononuclear Cu (II) terpyridine complexes: Impact of fused ring thiophene and thiazole head groups towards DNA/BSA interaction, cleavage and antiproliferative activity on HepG2 and triple negative CAL-51 cell line
Author
V.M. Manikandamathavan, M. Thangaraj, T. Weyhermuller, R.P. Parameswari, V. Punitha, N. Narasimha Murthy, Balachandran Unni Nair
Year
2017
Journal
European Journal of Medicinal Chemistry
Abstract
Two mononuclear copper (II) terpyridine complexes namely, [Cu(Btptpy) (ClO4)](ClO4) 1, and [Cu(Bttpy) (ClO4)](ClO4) 2, (Btptpy (L1) = 4’-(Benzothiophene)-2,2’:6′,2″-terpyridine, Bttpy (L2) = 4’-(Benzylthiazolyl)-2,2’:6′,2″-terpyridine) have been synthesized and characterized. Single crystal X-ray diffraction shows that, both ligands belong to monoclinic crystal system with space group P21/c (L1) and P21/n (L2). Absorption spectral titration, DNA melting study, circular dichroism and viscosity measurement reveal that, complex 1 and 2 bind with DNA through intercalation. In addition, interaction between the two copper (II) complexes and bovine serum albumin (BSA) has been studied by fluorescence titration, circular dichroism and their protease activity has been investigated using SDS-PAGE gel electrophoresis. PAGE and SDS-PAGE gel electrophoresis reveals both complexes have good nucleolytic and proteolytic property in the presence of additive hydrogen peroxide. Both complexes shows remarkable cytotoxic property against triple negative CAL-51 human breast cancer cell line and hepatocellular carcinoma (HepG2) cancer cell lines and bears very less cytotoxicity towards liver normal cell line (Changs). DCF-DA and TBRAS assay also supported that complex 1 and 2 induces elevated level of reactive oxygen species (ROS) and oxidative stress in cancer cells than normal cell line. Furthermore, FACS analysis confirms complex 1 and 2 brings apoptosis by growth phase cell cycle arrest.
Instrument
J-815
Keywords
Circular dichroism, DNA structure, Ligand binding, Biochemistry, Medicinal