Synthesis and comprehensive characterization with anticancer activity assessment of salicylaldehyde and 2-acetylphenol based chitosan thiosemicarbazones and their copper(II) complexes

Abstract

Functionalization of chitosan as salicylaldehyde and 2-acetylphenol-based chitosan thiosemicarbazone involving amino group at C2 position of pyranose ring was confirmed by comprehensive characterization by spectroscopic and analytical ways. Both the low molecular weight (Mw) chitosan oligosaccharide (CS) (Mw < 3000 Da, degree of deacetylation (DDA) = 87 %) and the crab shell chitosan (CCS) (Mw = 350 kDa, DDA = 67 %) functionalized thiosemicarbazones behaved as ONS tridentate ligand to form the square planar copper(II) complexes with a chloride ion as an additional ligand to satisfy the co-ordination sphere. All the derivatives were found thermally stable till the commencement of chitosan backbone disruption at 200 °C. The MTT assay profiles showed a conspicuous enhancement in the in vitro antitumorigenic and anticancer activity of native chitosan upon its functionalization as phenolic carbaldehyde chitosan thiosemicarbazones. Further, the assays more often revealed a further lowering of cell viability with chitosan oligosaccharide derivatives in comparison to high molecular weight chitosan derivatives, and a lower viability of the MCF-7 cancer cells than the tumorigenic MDCK cells. Both the low Mw chitosan with high DDA and high Mw chitosan with low DDA, the chitosan-functionalized salicylaldehyde based thiosemicarbazones, and their copper(II) chitosan thiosemicarbazone complexes were found to have minimal toxicity with IC50 >600 μgmL−1 against the mouse embryonic normal fibroblast NIH3T3 cells. These results were indicatives of more protonation and enhanced anticancer activity of chitosan oligosaccharide derivatives, and preferential cytotoxicity of chitosan biomaterials against the tumorigenic and cancer cells with more negatively charged cell surfaces.