Influence of anchoring moieties on new benzimidazole-based Schiff base copper(ii) complexes towards estrogen dependent breast cancer cells

Abstract

Two new benzimidazole Schiff base copper(ii) compounds [Cu(5-CH2PPh3-2-salmethylben)(NO3)(H2O)][BF4]·2/3(H2O)·1/3(MeOH) (1) and [Cu(5-CH2NEt3-2-salmethylben)(Cl)][BF4] (2) were synthesised by mixing 2-(1-methyl-1H-benzo[d]imidazol-2-yl)aniline, (3-formyl-4-hydroxybenzyl)triphenylphosphonium chloride or N,N-diethyl-N-(3-formyl-4-hydroxybenzyl)ethanaminium chloride and Cu(NO3)2·3H2O or CuCl2·2H2O in the presence of tetrafluoroborate in a binary mixture of MeOH : H2O under refluxing conditions. The structures of the compounds were established by elemental analysis, FT-IR, ESI-MS analytical techniques and, for 1, by single-crystal X-ray diffraction analysis. Absorption and fluorescence spectroscopic methods were performed to evaluate the calf thymus DNA interactions with the compounds. The calculated binding constants (Kb) of 3.14 × 105 M-1 for 1 and 3.20 × 105 M-1 for 2 were established. The intercalative DNA binding mode was also verified by molecular docking studies. Both compounds demonstrated a notable in vitro cytotoxic effect against human A-549 (lung carcinoma), MCF-7 (breast cancer) and HeLa (cervical cancer) cancer cell lines. A substantial repressive effect on the proliferation of MCF-7 cells (breast cancer cells) was observed for compound 1. The mechanism of action for the effective antiproliferative activity of 1 has additionally been confirmed by means of various biological studies such as morphological assessment through AO/EB, detection of apoptotic induction via Hoechst/PI dual staining, flow cytometry for detection of cell cycle arrest, quantitative analysis of apoptotic cells, DNA degradation, generation of reactive oxygen species (ROS) and by apoptotic induction through mitochondrial staining.