Antiproliferative activity and apoptosis induction, of organo-antimony(III)-copper(I) conjugates, against human breast cancer cells.

Abstract

Three known organo-antimony(III)-copper(I), mixed-metal small bioactive molecules (SBAMs) of formula [Cu(tpSb)3Cl] (1), [Cu2(tpSb)4Br2] (2) and [Cu2(tpSb)4I2] (3) (tpSb = triphenylstibine) were used for the clarification of their antiproliferative activity against human breast cancer cells: MCF-7 (hormone-dependent cells) and MDA-MB-231 (hormone-independent cells). The in vitro toxicity of 1-3 was studied against normal human foetal lung fibroblast cells (MRC-5). The genotoxicity of 1-3 was determined by the presence of micronucleus. The type of the cell death caused by 1-3 was determined using cell cycle arrest. The molecular mechanism of action of 1-3 was defined by their binding affinity towards CT-DNA (calf thymus DNA) using UV spectroscopy and viscosity measurements. Docking studies depict the interactions between 1-3 and DNA. Computations were also employed in order to rationalize the activity of these compounds. This is based on the contribution of metal aromaticity in the case of compounds 2 and 3 where the short Cu···Cu distance (2.7724(6) (2) and 2.7251(11) (3) Ǻ, respectively) suggests d10-d10 interaction between metal centres. The known small bioactive molecules of formula [Cu(tpSb)3Cl] (1), [Cu2(tpSb)4Br2] (2) and [Cu2(tpSb)4I2] (3) (tpSb = triphenylstibine) were used for the clarification of their antiproliferative activity against human breast cancer cells: MCF-7 (hormone-dependent (HD) cells) and MDA-MB-231 (hormone-independent (HI) cells).