Synthesis, Structure Elucidation by Multi-spectroscopic Techniques and Single-crystal X-ray Diffraction of Promising Fluoro/Bromo-substituted-chromone(bpy)copper(II) Anticancer Drug Entities

Abstract

Two fluoro/bromo substituted-chromone(bpy)copper(II) complexes of the formulae [Cu(L1)(bpy)(H2O)] 1 and [Cu(L2)(bpy)(NO3)] 2 where L1 = 6-fluoro-3-formylchromone, L2 = 6-bromo-3-formylchromone and bpy = 2,2′-bipyridine were prepared and characterized by multi-spectroscopic and single-crystal X-ray diffraction studies. Preliminary DNA binding profile of complexes 1 and 2 was determined by a battery of biophysical methods viz., UV–visible absorption, fluorescence, circular dichroic, cyclic voltammetry, and Raman spectroscopy which revealed their strong binding propensity by non-covalent ‘intercalation’ mode. The cleavage activity of 1 and 2 was performed by electrophoretic gel assay using pBR322 plasmid DNA, which demonstrated their efficient DNA cleaving ability at low micromolar concentrations (20 μM) via oxidative cleavage pathway. The anticancer screening data of 1 and 2 was performed against a panel of cancer strains {MCF-7, MDA-MB-231, Hop-62, AW13516 & SiHa} which revealed selective but good cytotoxic response against MCF-7 & MDA-MB-231, complex 2 exhibited higher potency than 1. Furthermore, cellular uptake studies of the complexes in MDA-MB-231 cancer cells were performed via confocal microscopy. Mechanistic oxidative stress assays namely, SOD, lipid peroxidation, and GSH deleption studies of both 1 and 2 were examined to validate the induced cell death phenomenon.