In Vitro Biomolecular Interaction Studies and Cytotoxic Activities of Newly Synthesised Copper(II) Complexes Bearing 2‐Hydroxynaphthaldehyde‐Based Thiosemicarbazone

• Published in: ChemistrySelect (Weinheim) 2018-07, Vol.3 (28), p.8118-8130
• Main Authors: Aneesrahman, K. N., Rohini, Gandhaveeti, Bhuvanesh, Nattamai S. P., Sundararaj, Sankaramanivel, Musthafa, Moideen, Sreekanth, Anandaram
• Format: Article
• Language: English
• Subjects: BSA; CT-DNA; Cytotoxicity; Flow cytometry; Thiosemicarbazone
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201800791

Two new thiosemicarbazone ligands of 2‐hydroxynaphthldehyde (L1 and L2) and their square planar Cu(II) complexes (C1 and C2) have been synthesised. The ligands and complexes were characterised by various spectroscopic technique (UV‐Visible spectra, FT IR (ATR), 1H & 13C NMR, ESI mass and EPR spectra). The molecular structure of ligands (L1 and L2) and complex (C2) were confirmed by single crystal X‐ray crystallography. C2 showed a slightly distorted square planar geometry. The in vitro DNA and protein (BSA) binding assay of these complexes were conducted using electronic absorption spectra and fluorescence spectra methods. In both cases, C2 showed stronger binding ability than C1. The in vitro cytotoxic activity of the Cu(II) complexes towards lung cancer (A549) cell line and human kidney (HEK‐293 T) cancer cell lines were investigated, where complex C2 showed high cytotoxicity while maintaining low toxicity towards non‐cancer originated cell line i. e., HEK‐293 T. The mechanism of cell death by complex C1 and C2 has been inspected using Acridine Orange/Ethidium Bromide (AO/EB) staining, flow cytometry and ROS generation studies. This study offers a new perspective on the role and importance of the terminal [N(4)] substitution of thiosemicarbazone on the medicinal properties of copper(II) thiosemicarbazone complexes. Two new square planar Cu(II) complexes (C1 and C2) of thiosemicarbazone ligands of 2‐hydroxynaphthldehyde (L1 and L2) have been synthesized and characterised. With the above complexes, diverse applications like In vitro biomolecular interaction studies of DNA/BSA and anticancer activity against lung cancer (A549) cell line and human kidney (HEK‐293 T) cancer cell lines were carried out and the structural activity relationship of the complexes were discussed