Copper(ii) complexes based on levofloxacin and 2N-donor ligands: synthesis, crystal structures and in vitro biological evaluation

March 24, 2020

Title

Copper(ii) complexes based on levofloxacin and 2N-donor ligands: synthesis, crystal structures and in vitro biological evaluation

Author

Manish Kumar, Gyanendra Kumar, Kanhaiya M. Dadure, Dhanraj T. Masram

Year

2019

Journal

New Journal of Chemistry

Abstract

Herein, we report the synthesis, molecular structures and bioevaluation of two different cationic copper(II) complexes with the third generation quinolone antibacterial agent levofloxacin (lvx) and 2N-substituted ligands 2,2′-dipyridylamine (bipyam) and bathophenanthroline (BPhen). The molecular structures of [Cu(lvx)(bipyam)Cl]+ (1) and [Cu(lvx)(BPhen)Cl]+ (2) exhibit distorted square-pyramidal coordination environments around the copper atoms with τ values of 0.137 in (1) and 0.0316 in (2). Their binding interaction modes towards calf-thymus (CT) DNA were examined by a series of spectroscopy measurements including electronic absorption, viscosity measurements, circular dichroism and fluorescence spectroscopy. Also, the quenching mechanism, thermodynamic parameters (ΔG°, ΔH° and ΔS°) and total number of binding sites per albumin (n) were explored at different temperatures (25, 30 and 35 °C) by fluorescence quenching experiments. These complexes quench the intrinsic fluorescence of serum albumins and complex 2 exhibits the highest binding constant values at 25 °C (KBSA = 7.77 ± 0.02 × 105 M−1 in the case of bovine serum albumin (BSA) and KHSA = 1.55 ± 0.01 × 105 M−1 in the case of human serum albumin (HSA)). Molecular docking simulations on the crystal structures of CT DNA, BSA and HSA were employed in order to study the ability of the complexes to bind to these target macromolecules. The in vitro bio-efficacies of the complexes were screened against nine different microorganisms to examine their antibacterial potential. Furthermore, the complexes were also subjected to cytotoxicity tests against the MCF-7 cancer cell line and the results indicated that both complexes have superior cytotoxicity to the currently used chemotherapeutic agent cisplatin.

Instrument

J-815

Keywords

Circular dichroism, DNA structure, Secondary structure, Ligand binding, Biochemistry