Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes: A study to understand their biological activity.

Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes: A study to understand their biological activity. J Inorg Biochem. 2014 Jul 23;140C:111-125 Authors: Bisceglie F, Pinelli S, Alinovi R, Goldoni M, Mutti A, Camerini A, Piola L, Tarasconi P, Pelosi G Abstract This paper reports the synthesis and characterization of trans-cinnamaldehyde thiosemicarbazone (Htcin), cuminaldehyde thiosemicarbazone (Htcum) and their copper and nickel complexes. All the compounds, which on healthy cells (human fibroblasts) show a neglectable cytotoxicity, were screened in vitro in cell line U937 for their antileukemic activity. These compounds, in spite of their molecular similarity, present variegated behaviors. Htcin shows no inhibition activity in U935 cells, while both its metal complexes inhibit proliferation with IC50 at μM concentrations. The other ligand, Htcum, and its metal complexes, besides inhibiting proliferation, induce apoptosis. The cell cycle analysis highlights a G2/M checkpoint stop suggesting a possible direct action on DNA or on topoisomerase IIa. From CD and UV spectroscopy experiments, the DNA results to be not the main target of all these molecules, while both copper complexes are effective topoisomerase IIa inhibitors. All of these molecules activate caspase-9 and caspase-3, while caspase-8 activity is significantly induced by both cinnamaldehyde metal complexes. Tests on PgP and intr...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research