Investigation on chloro-bridged binuclear copper(ii) complexes as potent metallodrug candidates against colon cancer via chemical and biological assessments

Abstract

In search of effective copper-based anticancer drug candidates, a new series of novel chloro-bridged binuclear copper(II) complexes of the type [Cu₂(L)₂(μ-Cl)₂] was synthesized through the metallation of benzoyl pyridine hydrazone ligands (HL1–HL5) with [Cu(DMSO)₂Cl₂]. Single-crystal X-ray diffraction data revealed that two copper metal centres were bridged through a pair of chloride ions making a square pyramidal geometry around each bivalent copper ion, which was further supported by spectral data. Properties of complexes 1–5, such as stability at biological pH and cellular uptake, were also assessed. The potential of these complexes to bind with DNA/BSA was promising with significant binding constant values in the range 10⁴–10⁶. A catechol oxidase enzyme mimicking activity study revealed that all the complexes can catalyse the conversion of 3,5-di-tert-butylcatechol (3,5-DTBC) into 3,5-tert-butylquinoline (3,5-DTBQ) under aerobic conditions. In addition, IC₅₀ values determined from the in vitro cytotoxicity of complexes 1–5 against colon cancer cells (HCT 116) and normal skin cells (L929) indicated that they possess appreciable cytotoxicity towards the former cells with an average concentration of 35 μM leaving the latter unaffected up to 200 μM (average). Acridine orange/ethidium bromide (AO/EB) dual-staining, reactive oxygen species (ROS) staining and mitochondrial membrane potential (MMP) assays were performed to assess the therapeutic efficacy of selective complexes against colon cancer cells, and an effective cell arresting ability of the complexes was observed. The results indicated that the synthesized complexes could be further exploited as novel therapeutic agents against cancer.