Synthesis and antiproliferative activity of novel organometallic cobalt(III) complex encapsulated in polydiacetylene-phospholipid nanoformulation

Abstract

Organometallic complexes are considered as promising anticancer agents with the aim to overcome the limitations of platinum drugs but until very recently the development of organometallic cobalt-based anticancer active compounds has remained scarce. Two novel half-sandwich Cobalt(III)-pentamethylcyclopentadienyl complexes containing Schiff base ligands of the general formula [Cp*Co(NN)CH3CN](ClO4)2(Cp*Co(L1) and Cp*Co(L2)), where Cp* is pentamethylcyclopentadiene and NN is bis(anthracen-9-ylmethylene)benzene-1,2-diamine (L1) or bis(4-isopropylbenzylidene)benzene-1,2-diamine (L2), have been synthesized and characterized by elemental analysis, spectroscopic techniques, DFT method and cyclic voltammogram analysis. The facile reduction behaviour of complexes illustrates the observed potency of their oxidative DNA cleavage. Cp*Co(L1) complex displays oxidative DNA cleavage in presence of ascorbic acid more prominent than Cp*Co(L2) by generating OH radicals. Cp*Co(L1) complex shows remarkable cytotoxicity (IC50: ∼0.5 μM) towards A549 lung and HeLaS3 cervical cancer cells but moderate to normal human lung fibroblast cells (IC50: 6.02 μM). Also, the cytotoxic potency of Cp*Co(L1) is significantly higher than its analogue complex as well as cis-platin due to its redox behaviour and enhanced hydrophobicity of the ligand moieties. The AO/EB staining assay reveals that the complexes are able to induce late apoptotic mode of cell death in lung and cervical cancer cells. In order to improve the biocompatibility and anticancer activity of Cp*Co(L1) complex, it is encapsulated into polymer-supported liposomes and the size and morphology of nanoformulation is characterized by suitable techniques. The toxic effect of the complex after being encapsulated into liposome is reduced towards normal cells. However, the nanoformulation is less active in lung and cervical cancer cells compared to non-encapsulated complex.